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3. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author

Mack, SC, Witt, H, Piro, RM, Gu, L, Zuyderduyn, S, Stütz, AM, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, DTW, Sill, M, Pugh, TJ, Ryzhova, M, Wani, KM, Shih, DJH, Head, R, Remke, M, Bailey, SD, Zichner, T, Faria, CC, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, AM, Northcott, PA, Peacock, J, Bertrand, KC, Agnihotri, S, Cavalli, FMG, Clarke, I, Nethery-Brokx, K, Creasy, CL, Verma, SK, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, MA, Roberts, SS, Fults, D, Massimi, L, Cho, YJ, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, AE, von Deimling, A, Witt, O, Scherer, SW, Fan, X, Muraszko, KM, Kool, M, Pomeroy, SL, Gupta, N, Phillips, J, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, PN, Weiss, WA, Jabado, N, Rutka, JT, Bouffet, E, Korbel, JO, Lupien, M, Aldape, KD, Bader, GD, Eils, R, Lichter, P, Dirks, PB, Pfister, SM, Korshunov, A, and Taylor, MD

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Pediatric, Human Genome, Rare Diseases, Animals, Brain Neoplasms, CpG Islands, DNA Methylation, Embryonic Stem Cells, Ependymoma, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Histones, Humans, Infant, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Phenotype, Polycomb Repressive Complex 2, Prognosis, Rhombencephalon, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014

4. How do parents and providers trade-off between disability and survival? Preferences in the treatment of pediatric medulloblastoma

Author

Khakban A, Mohammadi T, Lynd LD, Mabbott DJ, Bouffet E, Gastonguay L, Zafari Z, Malkin D, Taylor MD, and Marra CA

Subjects
Best Worst Scaling (BWS), Preference, Medulloblastoma, Trade-off, Cancer, Medicine (General), R5-920
Abstract

Amir Khakban,1 Tima Mohammadi,2 Larry D Lynd,1 Don J Mabbott,3,4 Eric Bouffet,5,6 Louise Gastonguay,1 Zafar Zafari,7 David Malkin,5,6 Michael D Taylor,8,9 Carlo A Marra10 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada; 2Centre for Health Evaluation and Outcome Sciences, University of British Columbia, St Paul’s Hospital, Vancouver, BC, Canada; 3Department of Psychology, University of Toronto, Toronto, ON, Canada; 4Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada; 5Department of Pediatrics, University of Toronto, Toronto, ON, Canada; 6Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; 7Health Policy and Management, Mailman School of Public Health, Columbia University, New York, NY, USA; 8Departments of Surgery, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; 9Department of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; 10School of Pharmacy, University of Otago, Dunedin, New Zealand Objective: The aim of this study was to determine the preferences of parents with children with medulloblastoma and clinicians who manage this condition and their trade-offs between survival and disability using a best–worst scaling (BWS) choice experiment. Methods: Mixed methods were used to develop a BWS tool. Health professionals involved in the care of medulloblastoma patients were contacted through oncology networks in Canada. Parents of children diagnosed with brain tumors were recruited via two clinics in Vancouver and Toronto. The profile case BWS was used with each participant completing 12 choice profiles with the respondent indicating the best and worst features of each profile. Surveys were stratified into good, moderate, and poor prognosis based on the probability of survival presented. Paired model conditional logit analysis was used to generate quantitative preferences. Results: Fifty-four parents (80% female) and 176 providers (36% female, 79% oncologists) participated in this study. There were many similarities in the parents’ and providers’ preferences for treatment although the parents tended to value survival higher than disability while providers seemed to value the opposite. Specifically, providers were willing to take more risk of recurrence in a child with good prognosis compared to intermediate and poor prognosis. Also, parents were less willing to take more survival risks than providers when they had to trade-off between mild disability and survival rate. Conclusion: This study provides useful insights into the preferences of parents and health care providers, the stakeholders of a collaborative decision for the treatment of pediatric medulloblastoma, and compares their values and trade-offs between different levels of survival and disability. Keywords: best–worst scaling, BWS, preference, medulloblastoma, trade-off, cancer

Published
2018

5. Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial.

Author

Daly, R, Hetherington, K, Hazell, E, Wadling, BR, Tyrrell, V, Tucker, KM, Marshall, GM, Ziegler, DS, Lau, LMS, Trahair, TN, O'Brien, TA, Collins, K, Gifford, AJ, Haber, M, Pinese, M, Malkin, D, Cowley, MJ, Karpelowsky, J, Drew, D, Jacobs, C, Wakefield, CE, Daly, R, Hetherington, K, Hazell, E, Wadling, BR, Tyrrell, V, Tucker, KM, Marshall, GM, Ziegler, DS, Lau, LMS, Trahair, TN, O'Brien, TA, Collins, K, Gifford, AJ, Haber, M, Pinese, M, Malkin, D, Cowley, MJ, Karpelowsky, J, Drew, D, Jacobs, C, and Wakefield, CE

Abstract

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia's first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care.

Published
2023

6. Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency

Author

Das, A, Sudhaman, S, Morgenstern, D, Coblentz, A, Chung, J, Stone, SC, Alsafwani, N, Liu, ZA, Abu Al Karsaneh, O, Soleimani, S, Ladany, H, Chen, D, Zatzman, M, Cabric, V, Nobre, L, Bianchi, V, Edwards, M, Nahum, LCS, Ercan, AB, Nabbi, A, Constantini, S, Dvir, R, Yalon-Oren, M, Campino, GA, Caspi, S, Larouche, V, Reddy, A, Osborn, M, Mason, G, Lindhorst, S, Bronsema, A, Magimairajan, V, Opocher, E, De Mola, RL, Sabel, M, Frojd, C, Sumerauer, D, Samuel, D, Cole, K, Chiaravalli, S, Massimino, M, Tomboc, P, Ziegler, DS, George, B, Van Damme, A, Hijiya, N, Gass, D, McGee, RB, Mordechai, O, Bowers, DC, Laetsch, TW, Lossos, A, Blumenthal, DT, Sarosiek, T, Yen, LY, Knipstein, J, Bendel, A, Hoffman, LM, Luna-Fineman, S, Zimmermann, S, Scheers, I, Nichols, KE, Zapotocky, M, Hansford, JR, Maris, JM, Dirks, P, Taylor, MD, Kulkarni, A, Shroff, M, Tsang, DS, Villani, A, Xu, W, Aronson, M, Durno, C, Shlien, A, Malkin, D, Getz, G, Maruvka, YE, Ohashi, PS, Hawkins, C, Pugh, TJ, Bouffet, E, Tabori, U, Das, A, Sudhaman, S, Morgenstern, D, Coblentz, A, Chung, J, Stone, SC, Alsafwani, N, Liu, ZA, Abu Al Karsaneh, O, Soleimani, S, Ladany, H, Chen, D, Zatzman, M, Cabric, V, Nobre, L, Bianchi, V, Edwards, M, Nahum, LCS, Ercan, AB, Nabbi, A, Constantini, S, Dvir, R, Yalon-Oren, M, Campino, GA, Caspi, S, Larouche, V, Reddy, A, Osborn, M, Mason, G, Lindhorst, S, Bronsema, A, Magimairajan, V, Opocher, E, De Mola, RL, Sabel, M, Frojd, C, Sumerauer, D, Samuel, D, Cole, K, Chiaravalli, S, Massimino, M, Tomboc, P, Ziegler, DS, George, B, Van Damme, A, Hijiya, N, Gass, D, McGee, RB, Mordechai, O, Bowers, DC, Laetsch, TW, Lossos, A, Blumenthal, DT, Sarosiek, T, Yen, LY, Knipstein, J, Bendel, A, Hoffman, LM, Luna-Fineman, S, Zimmermann, S, Scheers, I, Nichols, KE, Zapotocky, M, Hansford, JR, Maris, JM, Dirks, P, Taylor, MD, Kulkarni, A, Shroff, M, Tsang, DS, Villani, A, Xu, W, Aronson, M, Durno, C, Shlien, A, Malkin, D, Getz, G, Maruvka, YE, Ohashi, PS, Hawkins, C, Pugh, TJ, Bouffet, E, and Tabori, U

Abstract

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Published
2022

9. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, Tabori, U, Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, and Tabori, U

Abstract

PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

10. Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.

Author

Kim, J, Light, N, Subasri, V, Young, EL, Wegman-Ostrosky, T, Barkauskas, DA, Hall, D, Lupo, PJ, Patidar, R, Maese, LD, Jones, K, Wang, M, Tavtigian, SV, Wu, D, Shlien, A, Telfer, F, Goldenberg, A, Skapek, SX, Wei, JS, Wen, X, Catchpoole, D, Hawkins, DS, Schiffman, JD, Khan, J, Malkin, D, Stewart, DR, Kim, J, Light, N, Subasri, V, Young, EL, Wegman-Ostrosky, T, Barkauskas, DA, Hall, D, Lupo, PJ, Patidar, R, Maese, LD, Jones, K, Wang, M, Tavtigian, SV, Wu, D, Shlien, A, Telfer, F, Goldenberg, A, Skapek, SX, Wei, JS, Wen, X, Catchpoole, D, Hawkins, DS, Schiffman, JD, Khan, J, Malkin, D, and Stewart, DR

Abstract

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts. MATERIALS AND METHODS: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort. RESULTS: We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants (ATM, CDKN1C) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with FOXO1 fusion-negative RMS patients versus the patients with FOXO1 fusion-positive RMS. We identified pathogenic germline variants in CSGs previously (TP53, NF1, DICER1, mismatch repair genes), rarely (BRCA2, CBL, CHEK2, SMARCA4), or never (FGFR4) reported in RMS. Numerous genes (TP53, BRCA2, mismatch repair) were on the ACMG Secondary Findings 2.0 list. CONCLUSION: In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.

Published
2021

13. “Balancing Expectations with Actual Realities”: Conversations with Clinicians and Scientists in the First Year of a High-Risk Childhood Cancer Precision Medicine Trial

Author

McGill, BC, Wakefield, CE, Hetherington, K, Munro, LJ, Warby, M, Lau, L, Tyrrell, V, Ziegler, DS, O’brien, TA, Marshall, GM, Malkin, D, Hansford, JR, Tucker, KM, Vetsch, J, McGill, BC, Wakefield, CE, Hetherington, K, Munro, LJ, Warby, M, Lau, L, Tyrrell, V, Ziegler, DS, O’brien, TA, Marshall, GM, Malkin, D, Hansford, JR, Tucker, KM, and Vetsch, J

Abstract

Precision medicine is changing cancer care and placing new demands on oncology professionals. Precision medicine trials for high-risk childhood cancer exemplify these complexities. We assessed clinicians’ (n = 39) and scientists’ (n = 15) experiences in the first year of the PRecISion Medicine for Children with Cancer (PRISM) trial for children and adolescents with high-risk cancers, through an in-depth semi-structured interview. We thematically analysed participants’ responses regarding their professional challenges, and measured oncologists’ knowledge of genetics and confidence with somatic and germline molecular test results. Both groups described positive early experiences with PRISM but were cognisant of managing parents’ expectations. Key challenges for clinicians included understanding and communicating genomic results, balancing biopsy risks, and drug access. Most oncologists rated ‘good’ knowledge of genetics, but a minority were ‘very confident’ in interpreting (25%), explaining (34.4%) and making treatment recommendations (18.8%) based on somatic genetic test results. Challenges for scientists included greater emotional impact of their work and balancing translational outputs with academic productivity. Continued tracking of these challenges across the course of the trial, while assessing the perspectives of a wider range of stakeholders, is critical to drive the ongoing development of a workforce equipped to manage the demands of paediatric precision medicine.

Published
2020

14. Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort

Author

de Medeiros, CB, Moxon-Emre, I, Scantlebury, N, Malkin, D, Ramaswamy, V, Decker, A, Law, N, Kumabe, T, Leonard, J, Rubin, J, Jung, S, Kim, SK, Gupta, N, Weiss, W, Faria, CC, Vibhakar, R, Lafay-Cousin, L, Chan, J, Kros, J.M., Janzen, L, Taylor, MD, Bouffet, E, Mabbott, DJ, de Medeiros, CB, Moxon-Emre, I, Scantlebury, N, Malkin, D, Ramaswamy, V, Decker, A, Law, N, Kumabe, T, Leonard, J, Rubin, J, Jung, S, Kim, SK, Gupta, N, Weiss, W, Faria, CC, Vibhakar, R, Lafay-Cousin, L, Chan, J, Kros, J.M., Janzen, L, Taylor, MD, Bouffet, E, and Mabbott, DJ

Published
2020

18. Family history-taking practices and genetic confidence in primary and tertiary care providers for childhood cancer survivors

Author

Wakefield, CE, Quinn, VF, Fardell, JE, Signorelli, C, Tucker, KM, Patenaude, AF, Malkin, D, Walwyn, T, Alvaro, F, Cohn, RJ, Wakefield, CE, Quinn, VF, Fardell, JE, Signorelli, C, Tucker, KM, Patenaude, AF, Malkin, D, Walwyn, T, Alvaro, F, and Cohn, RJ

Abstract

Background: There is growing impetus for increased genetic screening in childhood cancer survivors. Family history-taking is a critical first step in determining survivors’ suitability. However, the family history-taking practices of providers of pediatric oncology survivorship care and the confidence of these providers to discuss cancer risks to relatives are unknown. Procedure: Fifty-four providers completed semistructured interviews in total, which included eight tertiary providers representing nine hospitals across two countries (63% male, 63% oncologists, 37% nurses) and 46 primary care providers (PCPs) nominated by a survivor (59% male, 35% regional practice). We used content analysis and descriptive statistics/regression to analyze the data. Results: Few tertiary (38%) or primary (35%) providers regularly collected survivors’ family histories, often relying on survivors/parents to initiate discussions. Providers mostly took two-generation pedigrees (63% tertiary and 81% primary). Primary providers focused on adult cancers. Lack of time, alternative priorities, and perceived lack of relevance were common barriers. Half of all tertiary providers felt moderately comfortable discussing genetic cancer risk to children of survivors (88% felt similarly discussing risks to other relatives). Most primary providers lacked confidence: 41% felt confident regarding risks to survivors’ children and 48% regarding risks to other relatives. Conclusions: While family history-taking will not identify all survivors suitable for genetics assessment, recommendations for regular history-taking are not being implemented in tertiary or primary care. Additional PCP-targeted genetic education is warranted given that they are well placed to review family histories of pediatric cancer survivors.

Published
2018

19. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort

Author

Waszak, SM, Northcott, PA, Buchhalter, I, Robinson, GW, Sutter, C, Groebner, S, Grund, KB, Brugières, L, Jones, DTW, Pajtler, KW, Morrissy, AS, Kool, M, Sturm, D, Chavez, L, Ernst, A, Brabetz, S, Hain, M, Zichner, T, Segura-Wang, M, Weischenfeldt, J, Rausch, T, Mardin, BR, Zhou, X, Baciu, C, Lawerenz, C, Chan, JA, Varlet, P, Guerrini-Rousseau, L, Fults, DW, Grajkowska, W, Hauser, P, Jabado, N, Ra, YS, Zitterbart, K, Shringarpure, SS, De La Vega, FM, Bustamante, CD, Ng, HK, Perry, A, MacDonald, TJ, Hernáiz Driever, P, Bendel, AE, Bowers, DC, McCowage, G, Chintagumpala, MM, Cohn, R, Hassall, T, Fleischhack, G, Eggen, T, Wesenberg, F, Feychting, M, Lannering, B, Schüz, J, Johansen, C, Andersen, TV, Röösli, M, Kuehni, CE, Grotzer, M, Kjaerheim, K, Monoranu, CM, Archer, TC, Duke, E, Pomeroy, SL, Shelagh, R, Frank, S, Sumerauer, D, Scheurlen, W, Ryzhova, MV, Milde, T, Kratz, CP, Samuel, D, Zhang, J, Solomon, DA, Marra, M, Eils, R, Bartram, CR, von Hoff, K, Rutkowski, S, Ramaswamy, V, Gilbertson, RJ, Korshunov, A, Taylor, MD, Lichter, P, Malkin, D, Gajjar, A, Korbel, JO, Pfister, SM, Waszak, SM, Northcott, PA, Buchhalter, I, Robinson, GW, Sutter, C, Groebner, S, Grund, KB, Brugières, L, Jones, DTW, Pajtler, KW, Morrissy, AS, Kool, M, Sturm, D, Chavez, L, Ernst, A, Brabetz, S, Hain, M, Zichner, T, Segura-Wang, M, Weischenfeldt, J, Rausch, T, Mardin, BR, Zhou, X, Baciu, C, Lawerenz, C, Chan, JA, Varlet, P, Guerrini-Rousseau, L, Fults, DW, Grajkowska, W, Hauser, P, Jabado, N, Ra, YS, Zitterbart, K, Shringarpure, SS, De La Vega, FM, Bustamante, CD, Ng, HK, Perry, A, MacDonald, TJ, Hernáiz Driever, P, Bendel, AE, Bowers, DC, McCowage, G, Chintagumpala, MM, Cohn, R, Hassall, T, Fleischhack, G, Eggen, T, Wesenberg, F, Feychting, M, Lannering, B, Schüz, J, Johansen, C, Andersen, TV, Röösli, M, Kuehni, CE, Grotzer, M, Kjaerheim, K, Monoranu, CM, Archer, TC, Duke, E, Pomeroy, SL, Shelagh, R, Frank, S, Sumerauer, D, Scheurlen, W, Ryzhova, MV, Milde, T, Kratz, CP, Samuel, D, Zhang, J, Solomon, DA, Marra, M, Eils, R, Bartram, CR, von Hoff, K, Rutkowski, S, Ramaswamy, V, Gilbertson, RJ, Korshunov, A, Taylor, MD, Lichter, P, Malkin, D, Gajjar, A, Korbel, JO, and Pfister, SM

Abstract

Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we co

Published
2018

21. Prognostic Value of Postoperative Blood Levels of Carcinoembryonic Antigen (CEA) in Breast Cancer

Author

Myers, R. E., Sutherland, D. J. A., Meakin, J. W., Malkin, D. G., Kellen, J. A., Malkin, A., Allfrey, V. G., editor, Allgöwer, M., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Della Porta, G., editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Kirsten, W. H., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Nakahara, W., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Taylor, R. M., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Bonadonna, Gianni, editor, Mathé, Georges, editor, and Salmon, Sydney E., editor

Published
1979
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23. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Author

Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, Huang, A, Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, and Huang, A

Abstract

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Published
2016

24. Cytogenetic prognostication within medulloblastoma subgroups

Author

Shih, DJH, Northcott, PA, Remke, M, Korshunov, A, Ramaswamy, V, Kool, M, Luu, B, Yao, Y, Wang, X, Dubuc, AM, Garzia, L, Peacock, J, Mack, SC, Wu, X, Rolider, A, Morrissy, AS, Cavalli, FMG, Jones, DTW, Zitterbart, K, Faria, CC, Schüller, U, Kren, L, Kumabe, T, Tominaga, T, Ra, YS, Garami, M, Hauser, P, Chan, JA, Robinson, S, Bognár, L, Klekner, A, Saad, AG, Liau, LM, Albrecht, S, Fontebasso, A, Cinalli, G, De Antonellis, P, Zollo, M, Cooper, MK, Thompson, RC, Bailey, S, Lindsey, JC, Di Rocco, C, Massimi, L, Michiels, EMC, Scherer, SW, Phillips, JJ, Gupta, N, Fan, X, Muraszko, KM, Vibhakar, R, Eberhart, CG, Fouladi, M, Lach, B, Jung, S, Wechsler-Reya, RJ, Fèvre-Montange, M, Jouvet, A, Jabado, N, Pollack, IF, Weiss, WA, Lee, JY, Cho, BK, Kim, SK, Wang, KC, Leonard, JR, Rubin, JB, De Torres, C, Lavarino, C, Mora, J, Cho, YJ, Tabori, U, Olson, JM, Gajjar, A, Packer, RJ, Rutkowski, S, Pomeroy, SL, French, PJ, Kloosterhof, NK, Kros, JM, Van Meir, EG, Clifford, SC, Bourdeaut, F, Delattre, O, Doz, FF, Hawkins, CE, Malkin, D, and Grajkowska, WA

Subjects
Male, Adolescent, Kruppel-Like Transcription Factors, Zinc Finger Protein Gli2, Risk Assessment, Proto-Oncogene Proteins c-myc, Cytogenetics, Young Adult, Risk Factors, Predictive Value of Tests, Biomarkers, Tumor, Humans, Hedgehog Proteins, Oncology & Carcinogenesis, Child, In Situ Hybridization, Fluorescence, Proportional Hazards Models, Chromosomes, Human, Pair 14, Oncology And Carcinogenesis, Chromosomes, Human, Pair 11, Gene Expression Profiling, Nuclear Proteins, Reproducibility of Results, Infant, Prognosis, Gene Expression Regulation, Neoplastic, Wnt Proteins, Tissue Array Analysis, Child, Preschool, Female, Medulloblastoma
Abstract

Purpose: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. © 2014 by American Society of Clinical Oncology.

Published
2014
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25. GE-09 * COMBINED HEREDITARY AND SOMATIC MUTATIONS OF REPLICATION ERROR REPAIR GENES RESULT IN RAPID ONSET OF ULTRA-HYPERMUTATED MALIGNANT BRAIN TUMORS IN CHILDREN

Author

Shlien, A., primary, Campbell, B. B., additional, de Borja, R., additional, Alexandrov, L. B., additional, Merino, D. M., additional, Remke, M., additional, Bakry, D., additional, Dirks, P., additional, Huang, A., additional, Grundy, R. G., additional, Durno, C., additional, Aronson, M., additional, Taylor, M. D., additional, Pursell, Z. F., additional, Pearson, C. E., additional, Malkin, D., additional, Bouffet, E., additional, Hawkins, C., additional, Campbell, P. J., additional, and Tabori, U., additional

Published
2015
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26. LG-01 * BRAF MUTATION AND CDKN2A DELETION DEFINE A CLINICALLY DISTINCT SUBGROUP OF CHILDHOOD SECONDARY HIGH-GRADE GLIOMA

Author

Mistry, M., primary, Zhukova, N., additional, Merico, D., additional, Rakopoulos, P., additional, Krishnatry, R., additional, Shago, M., additional, Stavropoulos, J., additional, Pole, J., additional, Ray, P., additional, Remke, M., additional, Buczkowicz, P., additional, Ramaswamy, V., additional, Shlien, A., additional, Rutka, J., additional, Dirks, P., additional, Taylor, M., additional, Malkin, D., additional, Bouffet, E., additional, Hawkins, C., additional, and Tabori, U., additional

Published
2015
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27. PM-10 * GENETICALLY ENGINEERED MOUSE MODELS OF CHOROID PLEXUS TUMORS

Author

Wang, J., primary, Merino, D., additional, Murphy, B., additional, Dhall, G., additional, Kiehna, E., additional, Judkins, A., additional, Ellison, D., additional, Eberhart, C., additional, Vandenberg, S., additional, Malkin, D., additional, Gilbertson, R., additional, Roussel, M., additional, and Wechsler-Reya, R., additional

Published
2015
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28. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

Author

Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, Shih, DJH, Baskin, B, Ray, PN, Bouffet, E, Dirks, P, von Bueren, AO, Pfaff, E, Korshunov, A, Jones, DTW, Northcott, PA, Kool, M, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognár, L, Cho, BK, Eberhart, CG, Conter, CF, Fouladi, M, French, PJ, Grajkowska, WA, Gupta, N, Hauser, P, Jabado, N, Vasiljevic, A, Jung, S, Kim, SK, Klekner, A, Kumabe, T, Lach, B, Leonard, JR, Liau, LM, Massimi, L, Pollack, IF, Ra, YS, Rubin, JB, Van Meir, EG, Wang, KC, Weiss, WA, Zitterbart, K, Bristow, RG, Alman, B, Hawkins, CE, Malkin, D, Clifford, SC, Pfister, SM, Taylor, MD, Tabori, U, Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, Shih, DJH, Baskin, B, Ray, PN, Bouffet, E, Dirks, P, von Bueren, AO, Pfaff, E, Korshunov, A, Jones, DTW, Northcott, PA, Kool, M, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognár, L, Cho, BK, Eberhart, CG, Conter, CF, Fouladi, M, French, PJ, Grajkowska, WA, Gupta, N, Hauser, P, Jabado, N, Vasiljevic, A, Jung, S, Kim, SK, Klekner, A, Kumabe, T, Lach, B, Leonard, JR, Liau, LM, Massimi, L, Pollack, IF, Ra, YS, Rubin, JB, Van Meir, EG, Wang, KC, Weiss, WA, Zitterbart, K, Bristow, RG, Alman, B, Hawkins, CE, Malkin, D, Clifford, SC, Pfister, SM, Taylor, MD, and Tabori, U

Abstract

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Published
2014

29. Processed pseudogenes acquired somatically during cancer development

Author

Cooke, S.L., Shlien, A., Marshall, J., Pipinikas, C.P., Martincorena, I., Tubio, J.M., Li, Y., Menzies, A., Mudie, L., Ramakrishna, M., Yates, L., Davies, H., Bolli, N., Bignell, G.R., Tarpey, P.S., Behjati, S., Nik-Zainal, S., Papaemmanuil, E., Teixeira, V.H., Raine, K., O'Meara, S., Dodoran, M.S., Teague, J.W., Butler, A.P., Iacobuzio-Donahue, C., Santarius, T., Grundy, R.G., Malkin, D., Greaves, M., Munshi, N., Flanagan, A.M., Bowtell, D., Martin, S., Larsimont, D., Reis-Filho, J.S., Boussioutas, A., Taylor, J.A., Hayes, N.D., Janes, S.M., Futreal, P.A., Stratton, M.R., McDermott, U., Campbell, P.J., Span, P.N., Sweep, C.G.J., et al., Cooke, S.L., Shlien, A., Marshall, J., Pipinikas, C.P., Martincorena, I., Tubio, J.M., Li, Y., Menzies, A., Mudie, L., Ramakrishna, M., Yates, L., Davies, H., Bolli, N., Bignell, G.R., Tarpey, P.S., Behjati, S., Nik-Zainal, S., Papaemmanuil, E., Teixeira, V.H., Raine, K., O'Meara, S., Dodoran, M.S., Teague, J.W., Butler, A.P., Iacobuzio-Donahue, C., Santarius, T., Grundy, R.G., Malkin, D., Greaves, M., Munshi, N., Flanagan, A.M., Bowtell, D., Martin, S., Larsimont, D., Reis-Filho, J.S., Boussioutas, A., Taylor, J.A., Hayes, N.D., Janes, S.M., Futreal, P.A., Stratton, M.R., McDermott, U., Campbell, P.J., Span, P.N., Sweep, C.G.J., and et al.

Abstract

Contains fulltext : 136602.pdf (publisher's version ) (Open Access), Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Published
2014

30. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer

Author

Ju, YSE, Alexandrov, LB, Gerstung, M, Martincorena, I, Nik-Zainal, S, Ramakrishna, M, Davies, HR, Papaemmanuil, E, Gundem, G, Shlien, A, Bolli, N, Behjati, S, Tarpey, PS, Nangalia, J, Massie, CE, Butler, AP, Teague, JW, Vassiliou, GS, Green, AR, Du, MQ, Unnikrishnan, A, Pimanda, JE, Teh, BTE, Munshi, N, Greaves, M, Vyas, P, El-Naggar, AK, Santarius, T, Collins, VP, Grundy, R, Taylor, JA, Hayes, DN, Malkin, D, Foster, CS, Warren, AY, Whitaker, HC, Brewer, D, Eeles, R, Cooper, C, Neal, D, Visakorpi, T, Isaacs, WB, Bova, GS, Flanagan, AM, Futreal, PA, Lynch, AG, Chinnery, PF, McDermott, U, Stratton, MR, Campbell, PJ, Ju, YSE, Alexandrov, LB, Gerstung, M, Martincorena, I, Nik-Zainal, S, Ramakrishna, M, Davies, HR, Papaemmanuil, E, Gundem, G, Shlien, A, Bolli, N, Behjati, S, Tarpey, PS, Nangalia, J, Massie, CE, Butler, AP, Teague, JW, Vassiliou, GS, Green, AR, Du, MQ, Unnikrishnan, A, Pimanda, JE, Teh, BTE, Munshi, N, Greaves, M, Vyas, P, El-Naggar, AK, Santarius, T, Collins, VP, Grundy, R, Taylor, JA, Hayes, DN, Malkin, D, Foster, CS, Warren, AY, Whitaker, HC, Brewer, D, Eeles, R, Cooper, C, Neal, D, Visakorpi, T, Isaacs, WB, Bova, GS, Flanagan, AM, Futreal, PA, Lynch, AG, Chinnery, PF, McDermott, U, Stratton, MR, and Campbell, PJ

Abstract

Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

Published
2014

31. Processed pseudogenes acquired somatically during cancer development

Author

Cooke, SL, Shlien, A, Marshall, J, Pipinikas, CP, Martincorena, I, Tubio, JMC, Li, Y, Menzies, A, Mudie, L, Ramakrishna, M, Yates, L, Davies, H, Bolli, N, Bignell, GR, Tarpey, PS, Behjati, S, Nik-Zainal, S, Papaemmanuil, E, Teixeira, VH, Raine, K, O'Meara, S, Dodoran, MS, Teague, JW, Butler, AP, Iacobuzio-Donahue, C, Santarius, T, Grundy, RG, Malkin, D, Greaves, M, Munshi, N, Flanagan, AM, Bowtell, D, Martin, S, Larsimont, D, Reis-Filho, JS, Boussioutas, A, Taylor, JA, Hayes, DN, Janes, SM, Futreal, PA, Stratton, MR, McDermott, U, Campbell, PJ, Cooke, SL, Shlien, A, Marshall, J, Pipinikas, CP, Martincorena, I, Tubio, JMC, Li, Y, Menzies, A, Mudie, L, Ramakrishna, M, Yates, L, Davies, H, Bolli, N, Bignell, GR, Tarpey, PS, Behjati, S, Nik-Zainal, S, Papaemmanuil, E, Teixeira, VH, Raine, K, O'Meara, S, Dodoran, MS, Teague, JW, Butler, AP, Iacobuzio-Donahue, C, Santarius, T, Grundy, RG, Malkin, D, Greaves, M, Munshi, N, Flanagan, AM, Bowtell, D, Martin, S, Larsimont, D, Reis-Filho, JS, Boussioutas, A, Taylor, JA, Hayes, DN, Janes, SM, Futreal, PA, Stratton, MR, McDermott, U, and Campbell, PJ

Abstract

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Published
2014

32. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Author

Mack, S, Mack, S, Witt, H, Piro, R, Gu, L, Zuyderduyn, S, Stütz, A, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, D, Sill, M, Pugh, T, Ryzhova, M, Wani, K, Shih, D, Head, R, Remke, M, Bailey, S, Zichner, T, Faria, C, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, A, Northcott, P, Peacock, J, Bertrand, K, Agnihotri, S, Cavalli, F, Clarke, I, Nethery-Brokx, K, Creasy, C, Verma, S, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, M, Roberts, S, Fults, D, Massimi, L, Cho, Y, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, A, von Deimling, A, Witt, O, Scherer, S, Fan, X, Muraszko, K, Kool, M, Pomeroy, S, Jabado, N, Rutka, J, Bouffet, E, Korbel, J, Lupien, M, Aldape, K, Bader, G, Eils, R, Lichter, P, Dirks, P, Pfister, S, Korshunov, A, Taylor, M, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, P, Gupta, Nalin, Phillips, Joanna, Weiss, William, Mack, S, Mack, S, Witt, H, Piro, R, Gu, L, Zuyderduyn, S, Stütz, A, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, D, Sill, M, Pugh, T, Ryzhova, M, Wani, K, Shih, D, Head, R, Remke, M, Bailey, S, Zichner, T, Faria, C, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, A, Northcott, P, Peacock, J, Bertrand, K, Agnihotri, S, Cavalli, F, Clarke, I, Nethery-Brokx, K, Creasy, C, Verma, S, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, M, Roberts, S, Fults, D, Massimi, L, Cho, Y, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, A, von Deimling, A, Witt, O, Scherer, S, Fan, X, Muraszko, K, Kool, M, Pomeroy, S, Jabado, N, Rutka, J, Bouffet, E, Korbel, J, Lupien, M, Aldape, K, Bader, G, Eils, R, Lichter, P, Dirks, P, Pfister, S, Korshunov, A, Taylor, M, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, P, Gupta, Nalin, Phillips, Joanna, and Weiss, William

Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014

33. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author

Mack, S. C., Witt, H., Piro, R. M., Gu, L., Zuyderduyn, S., Stütz, A. M., Wang, X., Gallo, M., Garzia, L., Zayne, K., Zhang, X., Ramaswamy, V., Jäger, N., Jones, D. T. W., Sill, M., Pugh, T. J., Ryzhova, M., Wani, K. M., Shih, D. J. H., Head, R., Remke, M., Bailey, S. D., Zichner, T., Faria, C. C., Barszczyk, M., Stark, S., Seker-Cin, H., Hutter, S., Johann, P., Bender, S., Hovestadt, V., Tzaridis, T., Dubuc, A. M., Northcott, P. A., Peacock, J., Bertrand, K. C., Agnihotri, S., Cavalli, F. M. G., Clarke, I., Nethery-Brokx, K., Creasy, C. L., Verma, S. K., Koster, J., Wu, X., Yao, Y., Milde, T., Sin-Chan, P., Zuccaro, J., Lau, L., Pereira, S., Castelo-Branco, P., Hirst, M., Marra, M. A., Roberts, S. S., Fults, D., Massimi, Luca, Cho, Y. J., Van Meter, T., Grajkowska, W., Lach, B., Kulozik, A. E., Von Deimling, A., Witt, O., Scherer, S. W., Fan, X., Muraszko, K. M., Kool, M., Pomeroy, S. L., Gupta, N., Phillips, J., Huang, A., Tabori, U., Hawkins, C., Malkin, D., Kongkham, P. N., Weiss, W. A., Jabado, N., Rutka, J. T., Bouffet, E., Korbel, J. O., Lupien, M., Aldape, K. D., Bader, G. D., Eils, R., Lichter, P., Dirks, P. B., Pfister, S. M., Korshunov, A., Taylor, M. D., Massimi, L., Mack, S. C., Witt, H., Piro, R. M., Gu, L., Zuyderduyn, S., Stütz, A. M., Wang, X., Gallo, M., Garzia, L., Zayne, K., Zhang, X., Ramaswamy, V., Jäger, N., Jones, D. T. W., Sill, M., Pugh, T. J., Ryzhova, M., Wani, K. M., Shih, D. J. H., Head, R., Remke, M., Bailey, S. D., Zichner, T., Faria, C. C., Barszczyk, M., Stark, S., Seker-Cin, H., Hutter, S., Johann, P., Bender, S., Hovestadt, V., Tzaridis, T., Dubuc, A. M., Northcott, P. A., Peacock, J., Bertrand, K. C., Agnihotri, S., Cavalli, F. M. G., Clarke, I., Nethery-Brokx, K., Creasy, C. L., Verma, S. K., Koster, J., Wu, X., Yao, Y., Milde, T., Sin-Chan, P., Zuccaro, J., Lau, L., Pereira, S., Castelo-Branco, P., Hirst, M., Marra, M. A., Roberts, S. S., Fults, D., Massimi, Luca, Cho, Y. J., Van Meter, T., Grajkowska, W., Lach, B., Kulozik, A. E., Von Deimling, A., Witt, O., Scherer, S. W., Fan, X., Muraszko, K. M., Kool, M., Pomeroy, S. L., Gupta, N., Phillips, J., Huang, A., Tabori, U., Hawkins, C., Malkin, D., Kongkham, P. N., Weiss, W. A., Jabado, N., Rutka, J. T., Bouffet, E., Korbel, J. O., Lupien, M., Aldape, K. D., Bader, G. D., Eils, R., Lichter, P., Dirks, P. B., Pfister, S. M., Korshunov, A., Taylor, M. D., and Massimi, L.

Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland. © 2014 Macmillan Publishers Limited.

Published
2014

35. BI-21 * BRAF MUTATION AND CDKN2A DELETIONS DEFINE A CLINICALLY DISTINCT SUBGROUP OF CHILDHOOD SECONDARY HIGH GRADE GLIOMA

Author

Mistry, M., primary, Zhukova, N., additional, Merico, D., additional, Rakopoulos, P., additional, Krishnatry, R., additional, Shago, M., additional, Stavropoulos, J., additional, Ray, P., additional, Mangerel, J., additional, Remke, M., additional, Buczkowicz, P., additional, Ramaswamy, V., additional, Rutka, J., additional, Dirks, P., additional, Taylor, M., additional, Bouffet, E., additional, Malkin, D., additional, Huang, A., additional, Hawkins, C., additional, and Tabori, U., additional

Published
2014
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36. GE-21 * DRASTIC GENOMIC DIVERGENCE OF RECURRENT MEDULLOBLASTOMA INVALIDATES TARGETED THERAPIES DISCOVERED AT DIAGNOSIS

Author

Morrissy, S., primary, Garzia, L., additional, Remke, M., additional, Ramaswamy, V., additional, Jorgensen, F., additional, Wu, X., additional, Shah, S., additional, Ma, Y., additional, Mungall, K., additional, Van Meter, T., additional, Cho, Y.-J., additional, Collins, P., additional, MacDonald, T., additional, Li, X.-N., additional, Moore, R., additional, Northcott, P., additional, Pfister, S., additional, Malkin, D., additional, Marra, M., additional, and Taylor, M., additional

Published
2014
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38. NEUROPSYCHOLOGY

Author

Boman, K. K., primary, Hornquist, L., additional, Rickardsson, J., additional, Lannering, B., additional, Gustafsson, G., additional, Pitchford, N., additional, Davis, E., additional, Walker, D., additional, Hoang, D. H., additional, Pagnier, A., additional, Cousin, E., additional, Guichardet, K., additional, Schiff, I., additional, Dubois-Teklali, F., additional, Krainik, A., additional, Lazar, M. B., additional, Resnik, K., additional, Olsson, I. T., additional, Perrin, S., additional, Burtscher, I. B., additional, Lundgren, J., additional, Kahn, A., additional, Johanson, A., additional, Korzeniewska, J., additional, Dembowska-Baginska, B., additional, Perek-Polnik, M., additional, Walsh, K., additional, Gioia, A., additional, Wells, E., additional, Packer, R., additional, de Speville, E. D., additional, Dufour, C., additional, Bolle, S., additional, Giraudat, K., additional, Longaud, A., additional, Kieffer, V., additional, Grill, J., additional, Puget, S., additional, Valteau-Couanet, D., additional, Hetz-Pannier, L., additional, Noulhiane, M., additional, Chieffo, D., additional, Tamburrini, G., additional, Caldarelli, M., additional, Di Rocco, C., additional, Margelisch, K., additional, Studer, M., additional, Steinlin, M., additional, Leibundgut, K., additional, Heinks, T., additional, Longaud-Vales, A., additional, Chevignard, M., additional, Pujet, S., additional, Sainte-Rose, C., additional, Dellatolas, G., additional, Kahalley, L., additional, Grosshans, D., additional, Paulino, A., additional, Ris, M. D., additional, Chintagumpala, M., additional, Okcu, F., additional, Moore, B., additional, Stancel, H., additional, Minard, C., additional, Guffey, D., additional, Mahajan, A., additional, Herrington, B., additional, Raiker, J., additional, Manning, E., additional, Criddle, J., additional, Karlson, C., additional, Guerry, W., additional, Finlay, J., additional, Sands, S., additional, Dockstader, C., additional, Skocic, J., additional, Bouffet, E., additional, Laughlin, S., additional, Tabori, U., additional, Mabbott, D., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Taylor, M. D., additional, Malkin, D., additional, Law, N., additional, Kumabe, T., additional, Leonard, J., additional, Rubin, J., additional, Jung, S., additional, Kim, S.-K., additional, Gupta, N., additional, Weiss, W., additional, Faria, C., additional, Vibhakar, R., additional, Spiegler, B., additional, Janzen, L., additional, Liu, F., additional, Decker, L., additional, Lemiere, J., additional, Vercruysse, T., additional, Haers, M., additional, Vandenabeele, K., additional, Geuens, S., additional, Jacobs, S., additional, Van Gool, S., additional, Riggs, L., additional, Piscione, J., additional, Timmons, B., additional, Cunningham, T., additional, Bartels, U., additional, Chakravarty, M., additional, Laperriere, N., additional, Pipitone, J., additional, Strother, D., additional, Hukin, J., additional, Fryer, C., additional, McConnell, D., additional, Secco, D. E., additional, Cappelletti, S., additional, Gentile, S., additional, Cacchione, A., additional, Del Bufalo, F., additional, Staccioli, S., additional, Spagnoli, A., additional, Messina, R., additional, Carai, A., additional, Marras, C. E., additional, Mastronuzzi, A., additional, Brinkman, T., additional, Armstrong, G., additional, Kimberg, C., additional, Gajjar, A., additional, Srivastava, D. K., additional, Robison, L., additional, Hudson, M., additional, Krull, K., additional, Hardy, K., additional, Hostetter, S., additional, Hwang, E., additional, Leiss, U., additional, Bemmer, A., additional, Pletschko, T., additional, Grafeneder, J., additional, Schwarzinger, A., additional, Deimann, P., additional, Slavc, I., additional, Batchelder, P., additional, Wilkening, G., additional, Hankinson, T., additional, Foreman, N., additional, and Handler, M., additional

Published
2014
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39. MEDULLOBLASTOMA

Author

Vaidyanathan, G., primary, Gururangan, S., additional, Bigner, D., additional, Zalutsky, M., additional, Morfouace, M., additional, Shelat, A., additional, Megan, J., additional, Freeman, B. B., additional, Robinson, S., additional, Throm, S., additional, Olson, J. M., additional, Li, X.-N., additional, Guy, K. R., additional, Robinson, G., additional, Stewart, C., additional, Gajjar, A., additional, Roussel, M., additional, Sirachainan, N., additional, Pakakasama, S., additional, Anurathapan, U., additional, Hansasuta, A., additional, Dhanachai, M., additional, Khongkhatithum, C., additional, Hongeng, S., additional, Feroze, A., additional, Lee, K.-S., additional, Gholamin, S., additional, Wu, Z., additional, Lu, B., additional, Mitra, S., additional, Cheshier, S., additional, Northcott, P., additional, Lee, C., additional, Zichner, T., additional, Lichter, P., additional, Korbel, J., additional, Wechsler-Reya, R., additional, Pfister, S., additional, Project, I. P. T., additional, Li, K. K.-W., additional, Xia, T., additional, Ma, F. M. T., additional, Zhang, R., additional, Zhou, L., additional, Lau, K.-M., additional, Ng, H.-K., additional, Lafay-Cousin, L., additional, Chi, S., additional, Madden, J., additional, Smith, A., additional, Wells, E., additional, Owens, E., additional, Strother, D., additional, Foreman, N., additional, Packer, R., additional, Bouffet, E., additional, Wataya, T., additional, Peacock, J., additional, Taylor, M. D., additional, Ivanov, D., additional, Garnett, M., additional, Parker, T., additional, Alexander, C., additional, Meijer, L., additional, Grundy, R., additional, Gellert, P., additional, Ashford, M., additional, Walker, D., additional, Brent, J., additional, Cader, F. Z., additional, Ford, D., additional, Kay, A., additional, Walsh, R., additional, Solanki, G., additional, Peet, A., additional, English, M., additional, Shalaby, T., additional, Fiaschetti, G., additional, Baulande, S., additional, Gerber, N., additional, Baumgartner, M., additional, Grotzer, M., additional, Hayase, T., additional, Kawahara, Y., additional, Yagi, M., additional, Minami, T., additional, Kanai, N., additional, Yamaguchi, T., additional, Gomi, A., additional, Morimoto, A., additional, Hill, R., additional, Kuijper, S., additional, Lindsey, J., additional, Schwalbe, E., additional, Barker, K., additional, Boult, J., additional, Williamson, D., additional, Ahmad, Z., additional, Hallsworth, A., additional, Ryan, S., additional, Poon, E., additional, Ruddle, R., additional, Raynaud, F., additional, Howell, L., additional, Kwok, C., additional, Joshi, A., additional, Nicholson, S. L., additional, Crosier, S., additional, Wharton, S., additional, Robson, K., additional, Michalski, A., additional, Hargrave, D., additional, Jacques, T., additional, Pizer, B., additional, Bailey, S., additional, Swartling, F., additional, Petrie, K., additional, Weiss, W., additional, Chesler, L., additional, Clifford, S., additional, Kitanovski, L., additional, Prelog, T., additional, Kotnik, B. F., additional, Debeljak, M., additional, Grotzer, M. A., additional, Gevorgian, A., additional, Morozova, E., additional, Kazantsev, I., additional, Iukhta, T., additional, Safonova, S., additional, Kumirova, E., additional, Punanov, Y., additional, Afanasyev, B., additional, Zheludkova, O., additional, Grajkowska, W., additional, Pronicki, M., additional, Cukrowska, B., additional, Dembowska-Baginska, B., additional, Lastowska, M., additional, Murase, A., additional, Nobusawa, S., additional, Gemma, Y., additional, Yamazaki, F., additional, Masuzawa, A., additional, Uno, T., additional, Osumi, T., additional, Shioda, Y., additional, Kiyotani, C., additional, Mori, T., additional, Matsumoto, K., additional, Ogiwara, H., additional, Morota, N., additional, Hirato, J., additional, Nakazawa, A., additional, Terashima, K., additional, Fay-McClymont, T., additional, Walsh, K., additional, Mabbott, D., additional, Sturm, D., additional, Northcott, P. A., additional, Jones, D. T. W., additional, Korshunov, A., additional, Pfister, S. M., additional, Kool, M., additional, Hooper, C., additional, Hawes, S., additional, Kees, U., additional, Gottardo, N., additional, Dallas, P., additional, Siegfried, A., additional, Bertozzi, A. I., additional, Sevely, A., additional, Loukh, N., additional, Munzer, C., additional, Miquel, C., additional, Bourdeaut, F., additional, Pietsch, T., additional, Dufour, C., additional, Delisle, M. B., additional, Kawauchi, D., additional, Rehg, J., additional, Finkelstein, D., additional, Zindy, F., additional, Phoenix, T., additional, Gilbertson, R., additional, Trubicka, J., additional, Borucka-Mankiewicz, M., additional, Ciara, E., additional, Chrzanowska, K., additional, Perek-Polnik, M., additional, Abramczuk-Piekutowska, D., additional, Jurkiewicz, D., additional, Luczak, S., additional, Kowalski, P., additional, Krajewska-Walasek, M., additional, Sheila, C., additional, Lee, S., additional, Foster, C., additional, Manoranjan, B., additional, Pambit, M., additional, Berns, R., additional, Fotovati, A., additional, Venugopal, C., additional, O'Halloran, K., additional, Narendran, A., additional, Hawkins, C., additional, Ramaswamy, V., additional, Taylor, M., additional, Singhal, A., additional, Hukin, J., additional, Rassekh, R., additional, Yip, S., additional, Singh, S., additional, Duhman, C., additional, Dunn, S., additional, Chen, T., additional, Rush, S., additional, Fuji, H., additional, Ishida, Y., additional, Onoe, T., additional, Kanda, T., additional, Kase, Y., additional, Yamashita, H., additional, Murayama, S., additional, Nakasu, Y., additional, Kurimoto, T., additional, Kondo, A., additional, Sakaguchi, S., additional, Fujimura, J., additional, Saito, M., additional, Arakawa, T., additional, Arai, H., additional, Shimizu, T., additional, Jurkiewicz, E., additional, Daszkiewicz, P., additional, Drogosiewicz, M., additional, Hovestadt, V., additional, Buchhalter, I., additional, Jager, N. N., additional, Stuetz, A., additional, Johann, P., additional, Schmidt, C., additional, Ryzhova, M., additional, Landgraf, P., additional, Hasselblatt, M., additional, Schuller, U., additional, Yaspo, M.-L., additional, von Deimling, A., additional, Eils, R., additional, Modi, A., additional, Patel, M., additional, Berk, M., additional, Wang, L.-x., additional, Plautz, G., additional, Camara-Costa, H., additional, Resch, A., additional, Lalande, C., additional, Kieffer, V., additional, Poggi, G., additional, Kennedy, C., additional, Bull, K., additional, Calaminus, G., additional, Grill, J., additional, Doz, F., additional, Rutkowski, S., additional, Massimino, M., additional, Kortmann, R.-D., additional, Lannering, B., additional, Dellatolas, G., additional, Chevignard, M., additional, Solecki, D., additional, McKinnon, P., additional, Olson, J., additional, Hayden, J., additional, Ellison, D., additional, Buss, M., additional, Remke, M., additional, Lee, J., additional, Caspary, T., additional, Castellino, R., additional, Sabel, M., additional, Gustafsson, G., additional, Fleischhack, G., additional, Benesch, M., additional, Navajas, A., additional, Reddingius, R., additional, Delisle, M.-B., additional, Lafon, D., additional, Sevenet, N., additional, Pierron, G., additional, Delattre, O., additional, Ecker, J., additional, Oehme, I., additional, Mazitschek, R., additional, Lodrini, M., additional, Deubzer, H. E., additional, Kulozik, A. E., additional, Witt, O., additional, Milde, T., additional, Patmore, D., additional, Boulos, N., additional, Wright, K., additional, Boop, S., additional, Janicki, T., additional, Burzynski, S., additional, Burzynski, G., additional, Marszalek, A., additional, Triscott, J., additional, Green, M., additional, Rassekh, S. R., additional, Toyota, B., additional, Dunham, C., additional, Dunn, S. E., additional, Liu, K.-W., additional, Pei, Y., additional, Genovesi, L., additional, Ji, P., additional, Davis, M., additional, Ng, C. G., additional, Cho, Y.-J., additional, Jenkins, N., additional, Copeland, N., additional, Wainwright, B., additional, Tang, Y., additional, Schubert, S., additional, Nguyen, B., additional, Masoud, S., additional, Lee, A., additional, Willardson, M., additional, Bandopadhayay, P., additional, Bergthold, G., additional, Atwood, S., additional, Whitson, R., additional, Qi, J., additional, Beroukhim, R., additional, Tang, J., additional, Oro, A., additional, Link, B., additional, Bradner, J., additional, Vallero, S. G., additional, Bertin, D., additional, Basso, M. E., additional, Milanaccio, C., additional, Peretta, P., additional, Cama, A., additional, Mussano, A., additional, Barra, S., additional, Morana, G., additional, Morra, I., additional, Nozza, P., additional, Fagioli, F., additional, Garre, M. L., additional, Darabi, A., additional, Sanden, E., additional, Visse, E., additional, Stahl, N., additional, Siesjo, P., additional, Vaka, D., additional, Vasquez, F., additional, Weir, B., additional, Cowley, G., additional, Keller, C., additional, Hahn, W., additional, Gibbs, I. C., additional, Partap, S., additional, Yeom, K., additional, Martinez, M., additional, Vogel, H., additional, Donaldson, S. S., additional, Fisher, P., additional, Perreault, S., additional, Guerrini-Rousseau, L., additional, Pujet, S., additional, Kieffer-Renaux, V., additional, Raquin, M. A., additional, Varlet, P., additional, Longaud, A., additional, Sainte-Rose, C., additional, Valteau-Couanet, D., additional, Staal, J., additional, Lau, L. S., additional, Zhang, H., additional, Ingram, W. J., additional, Cho, Y. J., additional, Hathout, Y., additional, Brown, K., additional, Rood, B. R., additional, Handler, M., additional, Hankinson, T., additional, Kleinschmidt-Demasters, B. K., additional, Hutter, S., additional, Jones, D. T., additional, Kagawa, N., additional, Hirayama, R., additional, Kijima, N., additional, Chiba, Y., additional, Kinoshita, M., additional, Takano, K., additional, Eino, D., additional, Fukuya, S., additional, Yamamoto, F., additional, Nakanishi, K., additional, Hashimoto, N., additional, Hashii, Y., additional, Hara, J., additional, Yoshimine, T., additional, Wang, J., additional, Guo, C., additional, Yang, Q., additional, Chen, Z., additional, Filipek, I., additional, Swieszkowska, E., additional, Tarasinska, M., additional, Perek, D., additional, Kebudi, R., additional, Koc, B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Wolff, J., additional, Darendeliler, E., additional, Kerl, K., additional, Gronych, J., additional, McGlade, J., additional, Endersby, R., additional, Hii, H., additional, Johns, T., additional, Sastry, J., additional, Murphy, D., additional, Ronghe, M., additional, Cunningham, C., additional, Cowie, F., additional, Jones, R., additional, Calisto, A., additional, Sangra, M., additional, Mathieson, C., additional, Brown, J., additional, Phuakpet, K., additional, Larouche, V., additional, Bartels, U., additional, Ishida, T., additional, Hasegawa, D., additional, Miyata, K., additional, Ochi, S., additional, Saito, A., additional, Kozaki, A., additional, Yanai, T., additional, Kawasaki, K., additional, Yamamoto, K., additional, Kawamura, A., additional, Nagashima, T., additional, Akasaka, Y., additional, Soejima, T., additional, Yoshida, M., additional, Kosaka, Y., additional, von Bueren, A., additional, Goschzik, T., additional, Kortmann, R., additional, von Hoff, K., additional, Friedrich, C., additional, Muehlen, A. z., additional, Warmuth-Metz, M., additional, Soerensen, N., additional, Deinlein, F., additional, Zwiener, I., additional, Faldum, A., additional, Kuehl, J., additional, KRAMER, K., additional, -Taskar, N. P., additional, Zanzonico, P., additional, Humm, J. L., additional, Wolden, S. L., additional, Cheung, N.-K. V., additional, Venkataraman, S., additional, Alimova, I., additional, Harris, P., additional, Birks, D., additional, Balakrishnan, I., additional, Griesinger, A., additional, Foreman, N. K., additional, Vibhakar, R., additional, Margol, A., additional, Robison, N., additional, Gnanachandran, J., additional, Hung, L., additional, Kennedy, R., additional, Vali, M., additional, Dhall, G., additional, Finlay, J., additional, Erdrich-Epstein, A., additional, Krieger, M., additional, Drissi, R., additional, Fouladi, M., additional, Gilles, F., additional, Judkins, A., additional, Sposto, R., additional, Asgharzadeh, S., additional, Peyrl, A., additional, Chocholous, M., additional, Holm, S., additional, Grillner, P., additional, Blomgren, K., additional, Azizi, A., additional, Czech, T., additional, Gustafsson, B., additional, Dieckmann, K., additional, Leiss, U., additional, Slavc, I., additional, Babelyan, S., additional, Dolgopolov, I., additional, Pimenov, R., additional, Mentkevich, G., additional, Gorelishev, S., additional, Laskov, M., additional, von Bueren, A. O., additional, Nowak, J., additional, Kortmann, R. D., additional, Mynarek, M., additional, Muller, K., additional, Gerber, N. U., additional, Ottensmeier, H., additional, Kwiecien, R., additional, Yankelevich, M., additional, Boyarshinov, V., additional, Glekov, I., additional, Ozerov, S., additional, Gorelyshev, S., additional, Popa, A., additional, Subbotina, N., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Bell, R., additional, Martinez, D., additional, Sullivan, L. M., additional, Santi, M., additional, Burger, P. C., additional, Taube, J. M., additional, Drake, C. G., additional, Pardoll, D. M., additional, Lim, M., additional, Li, L., additional, Wang, W.-G., additional, Pu, J.-X., additional, Sun, H.-D., additional, Ruggieri, R., additional, Symons, M. H., additional, Vanan, M. I., additional, Bolin, S., additional, Schumacher, S., additional, Zeid, R., additional, Yu, F., additional, Vue, N., additional, Gibson, W., additional, Paolella, B., additional, Swartling, F. J., additional, Kieran, M. W., additional, Bradner, J. E., additional, Maher, O., additional, Khatua, S., additional, Tarek, N., additional, Zaky, W., additional, Gupta, T., additional, Mohanty, S., additional, Kannan, S., additional, Jalali, R., additional, Kapitza, E., additional, Denkhaus, D., additional, Muhlen, A. z., additional, van Vuurden, D. G., additional, Garami, M., additional, Fangusaro, J., additional, Davidson, T. B., additional, da Costa, M. J. G., additional, Sterba, J., additional, Clifford, S. C., additional, Finlay, J. L., additional, Schmidt, R., additional, Felsberg, J., additional, Skladny, H., additional, Cremer, F., additional, Reifenberger, G., additional, Kunder, R., additional, Sridhar, E., additional, Moiyadi, A. A., additional, Goel, A., additional, Goel, N., additional, Shirsat, N., additional, Othman, R., additional, Storer, L., additional, Kerr, I., additional, Coyle, B., additional, Law, N., additional, Smith, M. L., additional, Greenberg, M., additional, Laughlin, S., additional, Malkin, D., additional, Liu, F., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Nasir, A., additional, Onion, D., additional, Lourdusamy, A., additional, Grabowska, A., additional, Cai, Y., additional, Bradshaw, T., additional, de Medeiros, R. S. S., additional, Beaugrand, A., additional, Soares, S., additional, Epelman, S., additional, Wang, W., additional, Sultan, M., additional, Wechsler-Reya, R. J., additional, Zapatka, M., additional, Radlwimmer, B., additional, Alderete, D., additional, Baroni, L., additional, Lubinieki, F., additional, Auad, F., additional, Gonzalez, M. L., additional, Puya, W., additional, Pacheco, P., additional, Aurtenetxe, O., additional, Gaffar, A., additional, Gros, L., additional, Cruz, O., additional, Calvo, C., additional, Shinojima, N., additional, Nakamura, H., additional, Kuratsu, J.-i., additional, Hanaford, A., additional, Eberhart, C., additional, Archer, T., additional, Tamayo, P., additional, Pomeroy, S., additional, Raabe, E., additional, De Braganca, K., additional, Gilheeney, S., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Dunkel, I., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Shih, D., additional, Wang, X., additional, Faria, C., additional, Raybaud, C., additional, Tabori, U., additional, Rutka, J., additional, Jacobs, S., additional, De Vathaire, F., additional, Diallo, I., additional, Llanas, D., additional, Verez, C., additional, Diop, F., additional, Kahlouche, A., additional, Puget, S., additional, Thompson, E., additional, Prince, E., additional, Amani, V., additional, Sin-Chan, P., additional, Lu, M., additional, Kleinman, C., additional, Spence, T., additional, Picard, D., additional, Ho, K. C., additional, Chan, J., additional, Majewski, J., additional, Jabado, N., additional, Dirks, P., additional, Huang, A., additional, Madden, J. R., additional, Donson, A. M., additional, Mirsky, D. M., additional, Dubuc, A., additional, Mack, S., additional, Gendoo, D., additional, Luu, B., additional, MacDonald, T., additional, Van Meter, T., additional, Croul, S., additional, Laureano, A., additional, Brugmann, W., additional, Denman, C., additional, Singh, H., additional, Huls, H., additional, Moyes, J., additional, Sandberg, D., additional, Silla, L., additional, Cooper, L., additional, and Lee, D., additional

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2014
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40. HIGH GRADE GLIOMAS AND DIPG

Author

Classen, C. F., primary, William, D., additional, Linnebacher, M., additional, Farhod, A., additional, Kedr, W., additional, Elsabe, B., additional, Fadel, S., additional, Van Gool, S., additional, De Vleeschouwer, S., additional, Koks, C., additional, Garg, A., additional, Ehrhardt, M., additional, Riva, M., additional, Agostinis, P., additional, Graf, N., additional, Yao, T.-W., additional, Yoshida, Y., additional, Zhang, J., additional, Ozawa, T., additional, James, D., additional, Nicolaides, T., additional, Kebudi, R., additional, Cakir, F. B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Darendeliler, E., additional, Al-Kofide, A., additional, Al-Shail, E., additional, Khafaga, Y., additional, Al-Hindi, H., additional, Dababo, M., additional, Haq, A. U., additional, Anas, M., additional, Barria, M. G., additional, Siddiqui, K., additional, Hassounah, M., additional, Ayas, M., additional, van Zanten, S. V., additional, Jansen, M., additional, van Vuurden, D., additional, Huisman, M., additional, Vugts, D., additional, Hoekstra, O., additional, van Dongen, G., additional, Kaspers, G., additional, Cockle, J., additional, Ilett, E., additional, Scott, K., additional, Bruning-Richardson, A., additional, Picton, S., additional, Short, S., additional, Melcher, A., additional, Benesch, M., additional, Warmuth-Metz, M., additional, von Bueren, A. O., additional, Hoffmann, M., additional, Pietsch, T., additional, Kortmann, R.-D., additional, Eyrich, M., additional, Rutkowski, S., additional, Fruhwald, M. C., additional, Faber, J., additional, Kramm, C., additional, Porkholm, M., additional, Valanne, L., additional, Lonnqvist, T., additional, Holm, S., additional, Lannering, B., additional, Riikonen, P., additional, Wojcik, D., additional, Sehested, A., additional, Clausen, N., additional, Harila-Saari, A., additional, Schomerus, E., additional, Thorarinsdottir, H. K., additional, Lahteenmaki, P., additional, Arola, M., additional, Thomassen, H., additional, Saarinen-Pihkala, U. M., additional, Kivivuori, S.-M., additional, Buczkowicz, P., additional, Hoeman, C., additional, Rakopoulos, P., additional, Pajovic, S., additional, Morrison, A., additional, Bouffet, E., additional, Bartels, U., additional, Becher, O., additional, Hawkins, C., additional, Gould, T. W. A., additional, Rahman, C. V., additional, Smith, S. J., additional, Barrett, D. A., additional, Shakesheff, K. M., additional, Grundy, R. G., additional, Rahman, R., additional, Barua, N., additional, Cronin, D., additional, Gill, S., additional, Lowisl, S., additional, Hochart, A., additional, Maurage, C.-A., additional, Rocourt, N., additional, Vinchon, M., additional, Kerdraon, O., additional, Escande, F., additional, Grill, J., additional, Pick, V. K., additional, Leblond, P., additional, Burzynski, G., additional, Janicki, T., additional, Burzynski, S., additional, Marszalek, A., additional, Ramani, N., additional, Zaky, W., additional, Kannan, G., additional, Morani, A., additional, Sandberg, D., additional, Ketonen, L., additional, Maher, O., additional, Corrales-Medina, F., additional, Meador, H., additional, Khatua, S., additional, Brassesco, M., additional, Delsin, L., additional, Roberto, G., additional, Silva, C., additional, Ana, L., additional, Rego, E., additional, Scrideli, C., additional, Umezawa, K., additional, Tone, L., additional, Kim, S. J., additional, Kim, C.-Y., additional, Kim, I.-A., additional, Han, J. H., additional, Choi, B.-S., additional, Ahn, H. S., additional, Choi, H. S., additional, Haque, F., additional, Layfield, R., additional, Grundy, R., additional, Gandola, L., additional, Pecori, E., additional, Biassoni, V., additional, Schiavello, E., additional, Chiruzzi, C., additional, Spreafico, F., additional, Modena, P., additional, Bach, F., additional, Pignoli, E., additional, Massimino, M., additional, Drogosiewicz, M., additional, Dembowska-Baginska, B., additional, Jurkiewicz, E., additional, Filipek, I., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Perek, D., additional, Bender, S., additional, Jones, D. T., additional, Warnatz, H.-J., additional, Hutter, B., additional, Zichner, T., additional, Gronych, J., additional, Korshunov, A., additional, Eils, R., additional, Korbel, J. O., additional, Yaspo, M.-L., additional, Lichter, P., additional, Pfister, S. M., additional, Yadavilli, S., additional, Becher, O. J., additional, Kambhampati, M., additional, Packer, R. J., additional, Nazarian, J., additional, Lechon, F. C., additional, Fowkes, L., additional, Khabra, K., additional, Martin-Retortillo, L. M., additional, Marshall, L. V., additional, Vaidya, S., additional, Koh, D.-M., additional, Leach, M. O., additional, Pearson, A. D., additional, Zacharoulis, S., additional, Schrey, D., additional, Barone, G., additional, Panditharatna, E., additional, Stampar, M., additional, Siu, A., additional, Gordish-Dressman, H., additional, Devaney, J., additional, Hwang, E. I., additional, Chung, A. H., additional, Mittapalli, R. K., additional, Elmquist, W. F., additional, Castel, D., additional, Debily, M.-A., additional, Philippe, C., additional, Truffaux, N., additional, Taylor, K., additional, Calmon, R., additional, Boddaert, N., additional, Le Dret, L., additional, Saulnier, P., additional, Lacroix, L., additional, Mackay, A., additional, Jones, C., additional, Puget, S., additional, Sainte-Rose, C., additional, Blauwblomme, T., additional, Varlet, P., additional, Entz-Werle, N., additional, Maugard, C., additional, Bougeard, G., additional, Nguyen, A., additional, Chenard, M. P., additional, Schneider, A., additional, Gaub, M. P., additional, Tsoli, M., additional, Vanniasinghe, A., additional, Luk, P., additional, Dilda, P., additional, Haber, M., additional, Hogg, P., additional, Ziegler, D., additional, Simon, S., additional, Monje, M., additional, Gurova, K., additional, Gudkov, A., additional, Zapotocky, M., additional, Churackova, M., additional, Malinova, B., additional, Zamecnik, J., additional, Kyncl, M., additional, Tichy, M., additional, Puchmajerova, A., additional, Stary, J., additional, Sumerauer, D., additional, Boult, J., additional, Vinci, M., additional, Perryman, L., additional, Box, G., additional, Jury, A., additional, Popov, S., additional, Ingram, W., additional, Eccles, S., additional, Robinson, S., additional, Emir, S., additional, Demir, H. A., additional, Bayram, C., additional, Cetindag, F., additional, Kabacam, G. B., additional, Fettah, A., additional, Li, J., additional, Jamin, Y., additional, Cummings, C., additional, Bamber, J., additional, Sinkus, R., additional, Nandhabalan, M., additional, Bjerke, L., additional, Burford, A., additional, von Bueren, A., additional, Baudis, M., additional, Clarke, P., additional, Collins, I., additional, Workman, P., additional, Olaciregui, N., additional, Mora, J., additional, Carcaboso, A., additional, Bullock, A., additional, Alonso, M., additional, de Torres, C., additional, Cruz, O., additional, Pencreach, E., additional, Moussalieh, F. M., additional, Guenot, D., additional, Namer, I., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Hamilton, R., additional, Panigrahy, A., additional, Potter, D., additional, Connelly, A., additional, Dibridge, S., additional, Whiteside, T., additional, Okada, H., additional, Ahsan, S., additional, Raabe, E., additional, Haffner, M., additional, Warren, K., additional, Quezado, M., additional, Ballester, L., additional, Eberhart, C., additional, Rodriguez, F., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Classen, C. F., additional, Hofmann, M., additional, Schmid, I., additional, Simon, T., additional, Maass, E., additional, Russo, A., additional, Fleischhack, G., additional, Becker, M., additional, Hauch, H., additional, Sander, A., additional, Grasso, C., additional, Berlow, N., additional, Liu, L., additional, Davis, L., additional, Huang, E., additional, Woo, P., additional, Tang, Y., additional, Ponnuswami, A., additional, Chen, S., additional, Huang, Y., additional, Hutt-Cabezas, M., additional, Dret, L., additional, Meltzer, P., additional, Mao, H., additional, Abraham, J., additional, Fouladi, M., additional, Svalina, M. N., additional, Wang, N., additional, Hulleman, E., additional, Li, X.-N., additional, Keller, C., additional, Spellman, P. T., additional, Pal, R., additional, Jansen, M. H. A., additional, Sewing, A. C. P., additional, Lagerweij, T., additional, Vuchts, D. J., additional, van Vuurden, D. G., additional, Caretti, V., additional, Wesseling, P., additional, Kaspers, G. J. L., additional, Cohen, K., additional, Pearl, M., additional, Kogiso, M., additional, Zhang, L., additional, Qi, L., additional, Lindsay, H., additional, Lin, F., additional, Berg, S., additional, Muscal, J., additional, Amayiri, N., additional, Tabori, U., additional, Campbel, B., additional, Bakry, D., additional, Aronson, M., additional, Durno, C., additional, Gallinger, S., additional, Malkin, D., additional, Qaddumi, I., additional, Musharbash, A., additional, Swaidan, M., additional, Al-Hussaini, M., additional, Shandilya, S., additional, McCully, C., additional, Murphy, R., additional, Akshintala, S., additional, Cole, D., additional, Macallister, R. P., additional, Cruz, R., additional, Widemann, B., additional, Salloum, R., additional, Smith, A., additional, Glaunert, M., additional, Ramkissoon, A., additional, Peterson, S., additional, Baker, S., additional, Chow, L., additional, Sandgren, J., additional, Pfeifer, S., additional, Popova, S., additional, Alafuzoff, I., additional, de Stahl, T. D., additional, Pietschmann, S., additional, Kerber, M. J., additional, Zwiener, I., additional, Henke, G., additional, Muller, K., additional, Sieow, N. Y.-F., additional, Hoe, R. H. M., additional, Tan, A. M., additional, Chan, M. Y., additional, Soh, S. Y., additional, Burrell, K., additional, Chornenkyy, Y., additional, Remke, M., additional, Golbourn, B., additional, Barzczyk, M., additional, Taylor, M., additional, Rutka, J., additional, Dirks, P., additional, Zadeh, G., additional, Agnihotri, S., additional, Hashizume, R., additional, Ihara, Y., additional, Andor, N., additional, Chen, X., additional, Lerner, R., additional, Huang, X., additional, Tom, M., additional, Solomon, D., additional, Mueller, S., additional, Petritsch, C., additional, Zhang, Z., additional, Gupta, N., additional, Waldman, T., additional, Dujua, A., additional, Co, J., additional, Hernandez, F., additional, Doromal, D., additional, Hegde, M., additional, Wakefield, A., additional, Brawley, V., additional, Grada, Z., additional, Byrd, T., additional, Chow, K., additional, Krebs, S., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Cornilleau, G., additional, Paulsson, J., additional, Andreiuolo, F., additional, Guerrini-Rousseau, L., additional, Geoerger, B., additional, Vassal, G., additional, Ostman, A., additional, Parsons, D. W., additional, Trevino, L. R., additional, Gao, F., additional, Shen, X., additional, Hampton, O., additional, Kosigo, M., additional, Baxter, P. A., additional, Su, J. M., additional, Chintagumpala, M., additional, Dauser, R., additional, Adesina, A., additional, Plon, S. E., additional, Wheeler, D. A., additional, Lau, C. C., additional, Gielen, G., additional, Muehlen, A. z., additional, Kwiecien, R., additional, Wolff, J., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Fangusaro, J., additional, Kieran, M., additional, Fontebasso, A., additional, Papillon-Cavanagh, S., additional, Schwartzentruber, J., additional, Nikbakht, H., additional, Gerges, N., additional, Fiset, P.-O., additional, Bechet, D., additional, Faury, D., additional, De Jay, N., additional, Ramkissoon, L., additional, Corcoran, A., additional, Jones, D., additional, Sturm, D., additional, Johann, P., additional, Tomita, T., additional, Nagib, M., additional, Bendel, A., additional, Goumnerova, L., additional, Bowers, D. C., additional, Leonard, J. R., additional, Rubin, J. B., additional, Alden, T., additional, DiPatri, A., additional, Browd, S., additional, Leary, S., additional, Jallo, G., additional, Prados, M. D., additional, Banerjee, A., additional, Carret, A.-S., additional, Ellezam, B., additional, Crevier, L., additional, Klekner, A., additional, Bognar, L., additional, Hauser, P., additional, Garami, M., additional, Myseros, J., additional, Dong, Z., additional, Siegel, P. M., additional, Gump, W., additional, Ayyanar, K., additional, Ragheb, J., additional, Krieger, M., additional, Kiehna, E., additional, Robison, N., additional, Harter, D., additional, Gardner, S., additional, Handler, M., additional, Foreman, N., additional, Brahma, B., additional, MacDonald, T., additional, Malkin, H., additional, Chi, S., additional, Manley, P., additional, Bandopadhayay, P., additional, Greenspan, L., additional, Ligon, A., additional, Albrecht, S., additional, Ligon, K. L., additional, Majewski, J., additional, Jabado, N., additional, Cordero, F., additional, Halvorson, K., additional, Taylor, I., additional, Hutt, M., additional, Weingart, M., additional, Price, A., additional, Kantar, M., additional, Onen, S., additional, Kamer, S., additional, Turhan, T., additional, Kitis, O., additional, Ertan, Y., additional, Cetingul, N., additional, Anacak, Y., additional, Akalin, T., additional, Ersahin, Y., additional, Mason, G., additional, Ho, C., additional, Crozier, F., additional, Vezina, G., additional, Packer, R., additional, Hwang, E., additional, Gilheeney, S., additional, Millard, N., additional, DeBraganca, K., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Donzelli, M., additional, Fischer, C., additional, Petriccione, M., additional, Dunkel, I., additional, Afzal, S., additional, Fleming, A., additional, Larouche, V., additional, Zelcer, S., additional, Johnston, D. L., additional, Kostova, M., additional, Mpofu, C., additional, Decarie, J.-C., additional, Strother, D., additional, Lafay-Cousin, L., additional, Eisenstat, D., additional, Fryer, C., additional, Hukin, J., additional, Hsu, M., additional, Lasky, J., additional, Moore, T., additional, Liau, L., additional, Davidson, T., additional, Prins, R., additional, Hassal, T., additional, Baugh, J., additional, Kirkendall, J., additional, Doughman, R., additional, Leach, J., additional, Jones, B., additional, Miles, L., additional, Hargrave, D., additional, Jacques, T., additional, Savage, S., additional, Saunders, D., additional, Wallace, R., additional, Flutter, B., additional, Morgenestern, D., additional, Blanco, E., additional, Howe, K., additional, Lowdell, M., additional, Samuel, E., additional, Michalski, A., additional, Anderson, J., additional, Arakawa, Y., additional, Umeda, K., additional, Watanabe, K.-i., additional, Mizowaki, T., additional, Hiraoka, M., additional, Hiramatsu, H., additional, Adachi, S., additional, Kunieda, T., additional, Takagi, Y., additional, Miyamoto, S., additional, Venneti, S., additional, Santi, M., additional, Felicella, M. M., additional, Sullivan, L. M., additional, Dolgalev, I., additional, Martinez, D., additional, Perry, A., additional, Lewis, P. W., additional, Allis, D. C., additional, Thompson, C. B., additional, and Judkins, A. R., additional

Published
2014
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41. Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary

Author

Gorlick, R., Anderson, P., Andrulis, I., Arndt, C., Beardsley, G. P., Bernstein, M., Bridge, J., Cheung, N. -K, Dome, J. S., Ebb, D., Gardner, T., Gebhardt, M., Grier, H., Hansen, M., John Healey, Helman, L., Hock, J., Houghton, J., Houghton, P., Huvos, A., Khanna, C., Kieran, M., Kleinerman, E., Ladanyi, M., Lau, C., Malkin, D., Marina, N., Meltzer, P., Meyers, P., Schofield, D., Schwartz, C., Smith, M. A., Toretsky, J., Tsokos, M., Wexler, L., Wigginton, J., Withrow, S., Schoenfeldt, M., and Anderson, B.

Subjects
Osteosarcoma, Neovascularization, Pathologic, Humans, Angiogenesis Inhibitors, Bone Neoplasms, Child
Abstract

Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.

Published
2003

42. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Author

Remke, M, Ramaswamy, V, Peacock, J, Shih, DJH, Koelsche, C, Northcott, PA, Hill, N, Cavalli, FMG, Kool, Mirjam, Wang, X, Mack, SC, Barszczyk, M, Morrissy, AS, Wu, XC, Agnihotri, S, Luu, B, Jones, DTW, Garzia, L, Dubuc, AM, Zhukova, N, Vanner, R, Kros, J.M., French, Pim, van Meir, EG, Vibhakar, R, Zitterbart, K, Chan, JA, Bognar, L, Klekner, A, Lach, B, Jung, S, Saad, AG, Albrecht, S, Liau, LM, Zollo, M, Cooper, MK, Thompson, RC, Delattre, OO, Bourdeaut, F, Doz, FF, Garami, M, Hauser, P, Carlotti, CG, Van Meter, TE, Massimi, L, Fults, D, Pomeroy, SL, Kumabe, T, Ra, YS, Leonard, JR, Elbabaa, SK, Mora, J, Rubin, JB, Cho, YJ, McLendon, RE, Bigner, DD, Eberhart, CG, Fouladi, M, Wechsler-Reya, RJ, Faria, CC, Croul, SE, Huang, A, Bouffet, E, Hawkins, CE, Dirks, PB, Weiss, WA, Schuller, U, Pollack, IF, Rutkowski, S, Meyronet, D, Jouvet, A, Fevre-Montange, M, Jabado, N, Perek-Polnik, M, Grajkowska, WA, Kim, SK, Rutka, JT, Malkin, D, Tabori, U, Pfister, SM, Korshunov, A, von Deimling, A, Taylor, MD, Remke, M, Ramaswamy, V, Peacock, J, Shih, DJH, Koelsche, C, Northcott, PA, Hill, N, Cavalli, FMG, Kool, Mirjam, Wang, X, Mack, SC, Barszczyk, M, Morrissy, AS, Wu, XC, Agnihotri, S, Luu, B, Jones, DTW, Garzia, L, Dubuc, AM, Zhukova, N, Vanner, R, Kros, J.M., French, Pim, van Meir, EG, Vibhakar, R, Zitterbart, K, Chan, JA, Bognar, L, Klekner, A, Lach, B, Jung, S, Saad, AG, Albrecht, S, Liau, LM, Zollo, M, Cooper, MK, Thompson, RC, Delattre, OO, Bourdeaut, F, Doz, FF, Garami, M, Hauser, P, Carlotti, CG, Van Meter, TE, Massimi, L, Fults, D, Pomeroy, SL, Kumabe, T, Ra, YS, Leonard, JR, Elbabaa, SK, Mora, J, Rubin, JB, Cho, YJ, McLendon, RE, Bigner, DD, Eberhart, CG, Fouladi, M, Wechsler-Reya, RJ, Faria, CC, Croul, SE, Huang, A, Bouffet, E, Hawkins, CE, Dirks, PB, Weiss, WA, Schuller, U, Pollack, IF, Rutkowski, S, Meyronet, D, Jouvet, A, Fevre-Montange, M, Jabado, N, Perek-Polnik, M, Grajkowska, WA, Kim, SK, Rutka, JT, Malkin, D, Tabori, U, Pfister, SM, Korshunov, A, von Deimling, A, and Taylor, MD

Abstract

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in < 5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes.

Published
2013

43. CONTRIBUTION OF DNA COPY-NUMBER VARIATION (CNV) TO CANCER SUSCEPTIBILITY AND LARGE-SCALE GENOME ALTERATIONS IN OSTEOSARCOMA (OS)

Author

Pasic, I, Shlien, A, Novokmet, A, Zhang, C, Tabori, U, Pinto, D, Scherer, S W, Malkin, D, Pasic, I, Shlien, A, Novokmet, A, Zhang, C, Tabori, U, Pinto, D, Scherer, S W, and Malkin, D

Abstract

Introduction: OS, a common Li-Fraumeni syndrome (LFS)-associated neoplasm, is a common bone malignancy of children and adolescents. Sporadic OS is also characterized by young age of onset and high genomic instability, suggesting a genetic contribution to disease. This study examined the contribution of novel DNA structural variation elements, CNVs, to OS susceptibility. Given our finding of excessive constitutional DNA CNV in LFS patients, which often coincide with cancer-related genes, we hypothesized that constitutional CNV may also provide clues about the aetiology of LFS-related sporadic neoplasms like OS. Methods: CNV in blood DNA of 26 patients with sporadic OS was compared to that of 263 normal control samples from the International HapMap project, as well as 62 local controls. Analysis was performed on DNA hybridized to Affymetrix genome-wide human SNP array 6.0 by Partek Genomic Suite. Results: There was no detectable difference in average number of CNVs, CNV length, and total structural variation (product of average CNV number and length) between individuals with OS and controls. While this data is preliminary (small sample size), it argues against the presence of constitutional genomic instability in individuals with sporadic OS. Conclusion: We found that the majority of tumours from patients with sporadic OS show CN loss at chr3q13.31, raising the possibility that chr3q13.31 may represent a “driver” region in OS aetiology. In at least one OS tumour, which displays CN loss at chr3q13.31, we demonstrate decreased expression of a known tumour suppressor gene located at chr3q13.31. We are investigating the role ofchr3q13.31 in development of OS.

Published
2008

44. PEDIATRICS CLINICAL RESEARCH

Author

Antony, R., primary, Zagardo, M., additional, Gujrati, M., additional, Lin, J., additional, Antony, R., additional, Al-Rahawan, M., additional, Broniscer, A., additional, Bhardwaj, R., additional, Hampton, C., additional, Ozols, V., additional, Chakravadhanula, M., additional, Bouffet, E., additional, Hawkins, C., additional, Scheinemann, K., additional, Zelcer, S., additional, Johnston, D., additional, Lafay-Cousin, L., additional, Larouche, V., additional, Jabado, N., additional, Carret, A. S., additional, Hukin, J., additional, Eisenstat, D., additional, Pond, G., additional, Poskitt, K., additional, Wilson, B., additional, Bartels, U., additional, Tabori, U., additional, Dhall, G., additional, Haley, K., additional, Finlay, J., additional, Rushing, T., additional, Sposto, R., additional, Seeger, R., additional, Garvin, J., additional, Rupani, K., additional, Stark, E., additional, Anderson, R., additional, Feldstein, N., additional, Grill, J., additional, Hargrave, D., additional, Massimino, M., additional, Jaspan, T., additional, Varlet, P., additional, Jones, C., additional, Morgan, P., additional, Le Deley, M. C., additional, Azizi, A., additional, Canete, A., additional, Saran, F., additional, Bachir, J., additional, Bubuteishvili-Pacaud, L., additional, Rousseau, R., additional, Vassal, G., additional, Gupta, S., additional, Robinson, N., additional, Dhir, N., additional, Wong, K., additional, Zhou, S., additional, Kumabe, T., additional, Kawaguchi, T., additional, Saito, R., additional, Kanamori, M., additional, Yamashita, Y., additional, Sonoda, Y., additional, Tominaga, T., additional, Miyagawa, T., additional, Nwachukwu, C., additional, Youland, R., additional, Laack, N., additional, Filipek, I., additional, Drogosiewicz, M., additional, Polnik, M. P.-, additional, Swieszkowska, E., additional, Dembowska-Baginska, B., additional, Jurkiewicz, E., additional, Perek, D., additional, Grajkowska, W., additional, Roszkowski, M., additional, Sobol, G., additional, Musiol, K., additional, Wachowiak, J., additional, Kazmierczak, B., additional, Pogorzelski, J. P. -, additional, Mlynarski, W., additional, Szewczyk, B. Z.-, additional, Wysocki, M., additional, Niedzielska, E., additional, Kowalczyk, J., additional, Slusarz, H. W. -, additional, Balwierz, W., additional, Czepko, E. Z. -, additional, Szolkiewicz, A., additional, Perek-Polnik, M., additional, Lastowska, M., additional, Chojnacka, M., additional, Tarasinska, M., additional, Perreault, S., additional, Chao, K., additional, Ramaswamy, V., additional, Shih, D., additional, Remke, M., additional, Luu, B., additional, Schubert, S., additional, Fisher, P., additional, Partap, S., additional, Vogel, H., additional, Taylor, M., additional, Goumnerova, L., additional, Cho, Y.-J., additional, Robison, N., additional, Brown, R., additional, Cloughesy, T., additional, Davidson, T. B., additional, Krieger, M., additional, Berger, M., additional, Perry, A., additional, Gilles, F., additional, Finlay, J. L., additional, Khemani, J., additional, Britt, B., additional, Grimm, J., additional, Ruge, M. I., additional, Blau, T., additional, Hafkemeyer, V., additional, Hamisch, C., additional, Klinger, K., additional, Simon, T., additional, Sadighi, Z., additional, Ellezam, B., additional, Guindani, M., additional, Ater, J., additional, Shimizu, Y., additional, Arai, H., additional, Miyajima, M., additional, Shimoji, K., additional, Kondo, A., additional, Shinohara, E., additional, Perkins, S., additional, DeWees, T., additional, Slavc, I., additional, Chocholous, M., additional, Leiss, U., additional, Haberler, C., additional, Peyrl, A., additional, Azizi, A. A., additional, Dieckmann, K., additional, Woehrer, A., additional, Dorfer, C., additional, Czech, T., additional, Spence, T., additional, Picard, D., additional, Barszczyk, M., additional, Kim, S.-K., additional, Ra, Y.-S., additional, Fangusaro, J., additional, Toledano, H., additional, Nakamura, H., additional, Fan, X., additional, Muraszko, K. M., additional, Ng, H.-K., additional, Halliday, W., additional, Shago, M., additional, Hawkins, C. E., additional, Huang, A., additional, Suzuki, M., additional, van Zanten, S. V., additional, Jansen, M., additional, van Vuurden, D., additional, Hulleman, E., additional, Idema, S., additional, Noske, D., additional, Wolf, N., additional, Hendrikse, H., additional, Vandertop, P., additional, Kaspers, G. J., additional, Muller, K., additional, Schlamann, A., additional, Warmuth-Metz, M., additional, Pietsch, T., additional, Pietschmann, S., additional, Kortmann, R.-D., additional, Kramm, C. M., additional, von Bueren, A. O., additional, Walston, S., additional, Williams, T., additional, Hamstra, D., additional, Oh, K., additional, Pelloski, C., additional, Zhukova, N., additional, Pole, J., additional, Mistry, M., additional, Fried, I., additional, Lapperiere, N., additional, Dirks, P., additional, An, J., additional, Alon, N., additional, Nathan, P., additional, Greenberg, M., additional, and Malkin, D., additional

Published
2013
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45. Genetic counselling and testing for susceptibility to breast, ovarian and colon cancer: where are we today?

Author

Cole, D E, Gallinger, S, McCready, D R, Rosen, B, Engel, J, and Malkin, D

Subjects
Male, Ovarian Neoplasms, Colonic Neoplasms, Mutation, Humans, Breast Neoplasms, Female, Genetic Counseling, Genetic Predisposition to Disease, Disease Susceptibility, Genetic Testing, Research Article
Abstract

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.

Published
1996

46. SV40-like sequences in human bone tumors

Author

Carbone, M., Rizzo, P., Procopio, A., Giuliano, M., Pass, H. I., Gebhardt, M. C., Mangham, C., Hansen, M., Malkin, D. F., Bushart, G., Pompetti, F., Piero Picci, Levine, A. S., Bergsagel, J. D., Garcea, R. L., Carbone, M, Rizzo, P, Procopio, A, Giuliano, Mariateresa, Pass, Hi, Gebhardt, Mc, Mangham, C, Hansen, M, Malkin, Df, Bushart, G, Pompetti, F, Picci, P, Levine, A, Bergsagel, Jd, and Garcea, Rl

Published
1996

47. BIOLOGY

Author

Kim, J. H., primary, Song, H. B., additional, Kim, D. H., additional, Park, K. D., additional, Kim, J. H., additional, Lee, B. J., additional, Khatua, S., additional, Kalkan, E., additional, Brown, R., additional, Pearlman, M., additional, Vats, T., additional, Abela, L., additional, Fiaschetti, G., additional, Shalaby, T., additional, Grunder, E., additional, Ma, M., additional, Grahlert, J., additional, Baumgartner, M., additional, Siler, U., additional, Nonoguchi, N., additional, Ohgaki, H., additional, Grotzer, M., additional, Adachi, J.-i., additional, Suzuki, T., additional, Fukuoka, K., additional, Yanagisawa, T., additional, Mishima, K., additional, Koga, T., additional, Matsutani, M., additional, Nishikawa, R., additional, Sardi, I., additional, Giunti, L., additional, Bresci, C., additional, Cardellicchio, S., additional, Da Ros, M., additional, Buccoliero, A. M., additional, Farina, S., additional, Arico, M., additional, Genitori, L., additional, Massimino, M., additional, Filippi, L., additional, Erdreich-Epstein, A., additional, Zhou, H., additional, Ren, X., additional, Schur, M., additional, Davidson, T. B., additional, Ji, L., additional, Sposto, R., additional, Asgharzadeh, S., additional, Tong, Y., additional, White, E., additional, Murugesan, M., additional, Nimmervoll, B., additional, Wang, M., additional, Marino, D., additional, Ellison, D., additional, Finkelstein, D., additional, Pounds, S., additional, Malkin, D., additional, Gilbertson, R., additional, Eden, C., additional, Ju, B., additional, Phoenix, T., additional, Poppleton, H., additional, Lessman, C., additional, Taylor, M., additional, la Marca, G., additional, Malvagia, S., additional, Fratoni, V., additional, Giovannini, M. G., additional, Giangaspero, F., additional, Badiali, M., additional, Gleize, V., additional, Paris, S., additional, Moi, L., additional, Elhouadani, S., additional, Arcella, A., additional, Morace, R., additional, Antonelli, M., additional, Buttarelli, F., additional, Mokhtari, K., additional, Sanson, M., additional, Smith, S., additional, Ward, J., additional, Wilson, M., additional, Rahman, C., additional, Rose, F., additional, Peet, A., additional, Macarthur, D., additional, Grundy, R., additional, Rahman, R., additional, Venkatraman, S., additional, Birks, D., additional, Balakrishnan, I., additional, Alimova, I., additional, Harris, P., additional, Patel, P., additional, Foreman, N., additional, Vibhakar, R., additional, Wu, H., additional, Zhou, Q., additional, Wang, D., additional, Wang, G., additional, Dang, D., additional, Pencreach, E., additional, Nguyen, A., additional, Guerin, E., additional, Lasthaus, C., additional, Guenot, D., additional, Entz-Werle, N., additional, Unland, R., additional, Schlosser, S., additional, Farwick, N., additional, Plagemann, T., additional, Richter, G., additional, Juergens, H., additional, Fruehwald, M., additional, Chien, C.-L., additional, Lee, Y.-H., additional, Lin, C.-I., additional, Hsieh, J.-Y., additional, Lin, S.-C., additional, Wong, T.-T., additional, Ho, D. M.-T., additional, Wang, H.-W., additional, Lagah, S., additional, Tan, I.-L., additional, Malcolm, S., additional, Majani, Y., additional, van Vuurden, D. G., additional, Aronica, E., additional, Wedekind, L. E., additional, Hulleman, E., additional, Biesmans, D., additional, Bugiani, M., additional, Vandertop, W. P., additional, Kaspers, G. J. L., additional, Wurdinger, T., additional, Noske, D. P., additional, Van der Stoop, P. M., additional, Shukla, S., additional, Kuipers, G. K., additional, Slotman, B. J., additional, Cloos, J., additional, Sun, T., additional, Warrington, N., additional, Luo, J., additional, Ganzhorn, S., additional, Tabori, U., additional, Druley, T., additional, Gutmann, D., additional, Rubin, J., additional, Castelo-Branco, P., additional, Choufani, S., additional, Mack, S., additional, Galagher, D., additional, Zhang, C., additional, Lipman, T., additional, Zhukova, N., additional, Martin, D., additional, Merino, D., additional, Wasserman, J., additional, Samuel, C., additional, Alon, N., additional, Hitzler, J., additional, Wang, J. C. Y., additional, Keller, G., additional, Dirks, P. B., additional, Pfister, S., additional, Taylor, M. D., additional, Weksberg, R., additional, Leblond, P., additional, Meignan, S., additional, Dewitte, A., additional, Le Tinier, F., additional, Wattez, N., additional, Lartigau, E., additional, Lansiaux, A., additional, Hanson, R., additional, Gordon, I., additional, Zhao, S., additional, Camphausen, K., additional, Warren, K., additional, Warrington, N. M., additional, Gutmann, D. H., additional, Rubin, J. B., additional, Jaillet, M., additional, Kovacs, Z., additional, Martin-Fiori, E., additional, Bernasconi, M., additional, Werner, B., additional, Dyberg, C., additional, Baryawno, N., additional, Milosevic, J., additional, Wickstrom, M., additional, Northcott, P. A., additional, Kool, M., additional, Kogner, P., additional, Johnsen, J. I., additional, Reynolds, G., additional, Davies, N., additional, Arvanitis, T., additional, Zoghbi, A., additional, Meisterernst, M., additional, Fruehwald, M. C., additional, Kerl, K., additional, Orr, B., additional, Haffner, M., additional, Nelson, W., additional, Yegnasubramanian, S., additional, Eberhart, C., additional, Fotovati, A., additional, Abu-Ali, S., additional, Wang, P.-S., additional, Deleyrolle, L., additional, Lee, C., additional, Triscott, J., additional, Chen, J., additional, Franciosi, S., additional, Nakamura, Y., additional, Sugita, Y., additional, Uchiumi, T., additional, Kuwano, M., additional, Leavitt, B., additional, Singh, S., additional, Jury, A., additional, Jones, C., additional, Wakimoto, H., additional, Reynolds, B., additional, Pallen, C., additional, Dunn, S., additional, Fletcher, S., additional, Levine, J., additional, Li, M., additional, Kagawa, N., additional, Hirayama, R., additional, Chiba, Y., additional, Kijima, N., additional, Arita, H., additional, Kinoshita, M., additional, Hashimoto, N., additional, Izumoto, S., additional, Maruno, M., additional, and Yoshimine, T., additional

Published
2012
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48. NEUROPSYCHOLOGY

Author

Brinkman, T., primary, Liu, W., additional, Armstrong, G., additional, Gajjar, A., additional, Merchant, T., additional, Kimberg, C., additional, Kun, L., additional, Srivastava, D. K., additional, Gurney, J., additional, Robison, L., additional, Hudson, M., additional, Krull, K., additional, Rubens, J., additional, Lulla, R. R., additional, Lai, J.-S., additional, Fangusaro, J., additional, Wolfe, K., additional, Madan-Swain, A., additional, Reddy, A., additional, Hunter, G., additional, Banos, J., additional, Kana, R., additional, Resch, A., additional, von Hoff, K., additional, von Buren, A. O., additional, Friedrich, C., additional, Treulieb, W., additional, Lindow, C., additional, Kwiecien, R., additional, Ottensmeier, H., additional, Rutkowski, S., additional, Armstrong, C. L., additional, Phillips, P. C., additional, Lustig, R. A., additional, Stamos, C., additional, Li, Y., additional, Belasco, J., additional, Minturn, J. E., additional, Fisher, M. J., additional, Heinks-Maldonado, T., additional, Wingeier, K., additional, Lory, V., additional, Schafer, C., additional, Studer, M., additional, Steinlin, M., additional, Leibundgut, K., additional, de Ruiter, M., additional, Schouten, N., additional, Greidanus, J., additional, Grootenhuis, M., additional, Oosterlaan, J., additional, A, A. L.-V., additional, Grill, J., additional, Puget, S., additional, Sainte-Rose, C., additional, Dufour, C., additional, Kieffer, V., additional, Dellatolas, G., additional, -Shkedi, E. B., additional, Ben Arush, M. W., additional, Kaplinsky, H., additional, Ash, S., additional, Goshen, Y., additional, Yaniv, I., additional, Cohen, I. J., additional, Levy, J. M., additional, Tello, T., additional, Lu, X., additional, Gao, D., additional, Wilkening, G., additional, Donson, A., additional, Foreman, N., additional, Liu, A., additional, Korzeniewska, J., additional, Baginska, B. D., additional, Perek, D., additional, Staccioli, S., additional, Chieffo, D., additional, Petrarca, M., additional, Moxon-Emre, I., additional, Taylor, M., additional, Bouffet, E., additional, Malkin, D., additional, Hawkins, C., additional, Scantlebury, N., additional, Mabbott, D., additional, Cunningham, T., additional, Piscione, J., additional, Igoe, D., additional, Orfus, M., additional, Bartels, U., additional, Laughlin, S., additional, Tabori, U., additional, Hardy, K., additional, Carlson-Green, B., additional, Conklin, H., additional, Dockstader, C., additional, Wang, F., additional, Bostan, S., additional, Liu, F., additional, Zou, P., additional, Conklin, H. M., additional, Mulhern, R. K., additional, Butler, R. W., additional, Ogg, R. J., additional, Diver, T., additional, Manley, P., additional, Kieran, M., additional, Chordas, C., additional, Liptak, C., additional, Delaney, B., additional, Brand, S., additional, and Rey-Casserly, C., additional

Published
2012
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49. RARE TUMORS

Author

Kiyotani, C., primary, Uno, T., additional, Ogiwara, H., additional, Morota, N., additional, Nakazawa, A., additional, Tsutsumi, Y., additional, Masaki, H., additional, Mori, T., additional, Sanz, J. A. S., additional, Guibelalde, M., additional, Tavera, A., additional, Herandez, I., additional, Ibanez, J., additional, Brell, M., additional, Mas, A., additional, Muller, H. L., additional, Gebhardt, U., additional, Warmuth-Metz, M., additional, Pietsch, T., additional, Sorensen, N., additional, Kortmann, R.-D., additional, Stapleton, S., additional, Gonzalez, I., additional, Steinbrueck, S., additional, Rodriguez, L., additional, Tuite, G., additional, Krzyzankova, M., additional, Mertsch, S., additional, Jeibmann, A., additional, Kordes, U., additional, Wolff, J., additional, Paulus, W., additional, Hasselblatt, M., additional, Nonaka, Y., additional, Hara, S., additional, Fukazawa, S., additional, Shimizu, K., additional, Ben-Arush, M., additional, Postovsky, S., additional, Toledano, H., additional, Peretz-Nahum, M., additional, Fujimura, J., additional, Sakaguchi, S., additional, Kondo, A., additional, Saito, Y., additional, Shimoji, K., additional, Ohara, Y., additional, Arakawa, A., additional, Saito, M., additional, Shimizu, T., additional, Benesch, M., additional, von Bueren, A. O., additional, Dantonello, T., additional, von Hoff, K., additional, Leuschner, I., additional, Claviez, A., additional, Bierbach, U., additional, Kropshofer, G., additional, Korinthenberg, R., additional, Graf, N., additional, Suttorp, M., additional, Kortmann, R. D., additional, Friedrich, C., additional, Klingebiel, T., additional, Koscielniak, E., additional, Rutkowski, S., additional, Mesa, M., additional, Sanchez, M., additional, Mejia, J., additional, Pena, G., additional, Dussan, R., additional, Cabeza, M., additional, Storino, A., additional, Dincer, F., additional, Roffidal, T., additional, Powell, M., additional, Berrak, S., additional, Wolff, J. E., additional, Fouyssac, F., additional, Delaunay, C., additional, Vignaud, J.-M., additional, Schmitt, E., additional, Klein, O., additional, Mansuy, L., additional, Chastagner, P., additional, Cruz, O., additional, Guillen, A., additional, Garcia, G., additional, Alamar, M., additional, Candela, S., additional, Roussos, I., additional, Garzon, M., additional, Sunol, M., additional, Muchart, J., additional, Rebollo, M., additional, Mora, J., additional, Diez, B., additional, Muggeri, A., additional, Arakaki, N., additional, Meli, F., additional, Sevlever, G., additional, Tsitouras, V., additional, Pettorini, B., additional, Fellows, G., additional, Blair, J., additional, Didi, M., additional, Daousi, C., additional, Steele, C., additional, Javadpour, M., additional, Sinha, A., additional, Hishii, M., additional, Ishii, H., additional, Miyajima, M., additional, Arai, H., additional, Dvir, R., additional, Sayar, D., additional, Levin, D., additional, Ben-Sirah, L., additional, Constantini, S., additional, Elhasid, R., additional, Gertsch, E., additional, Foreman, N., additional, Valera, E. T., additional, Brassesco, M. S., additional, Machado, H. R., additional, Oliveira, R. S., additional, Santos, A. C., additional, Terra, V. C., additional, Barros, M. V., additional, Scrideli, C. A., additional, Tone, L. G., additional, Merino, D., additional, Pienkowska, M., additional, Shlien, A., additional, Tabori, U., additional, Gilbertson, R., additional, Malkin, D., additional, Jeeva, I., additional, Chang, B., additional, Long, V., additional, Picton, S., additional, Burton, D., additional, Clark, S., additional, Kwok, C., additional, Mokete, B., additional, Rafiq, O., additional, Simmons, I., additional, Shing, M. M. K., additional, Li, C. K., additional, Chan, G. C. F., additional, Ha, S. Y., additional, Yuen, H. L., additional, Luk, C. W., additional, Ling, S. C., additional, Li, R. C. H., additional, Yoon, J. H., additional, Park, H. J., additional, Shin, H. J., additional, Park, B.-K., additional, Kim, J.-Y., additional, Jung, H. L., additional, Ra, Y. S., additional, Ghim, T. T., additional, Hartung, S., additional, Garami, M., additional, Traunecker, H., additional, Thall, P., additional, Mahajan, A., additional, Sumerauer, D., additional, Grillner, P., additional, Orrego, A., additional, Mosskin, M., additional, Gustavsson, B., additional, Holm, S., additional, Peters, N., additional, Rogers, M., additional, Chowdry, S., additional, Selman, W., additional, Mitchell, A., additional, Bangert, B., additional, Ahuja, S., additional, Laschinger, K., additional, Gold, D., additional, Stearns, D., additional, Wright, K., additional, Gupta, K., additional, Klimo, P., additional, Ellison, D., additional, Keating, G., additional, Eckel, L., additional, Giannini, C., additional, Wetjen, N., additional, Patton, A., additional, Zaky, W., additional, McComb, G., additional, Finlay, J., additional, Grimm, J., additional, Wong, K., additional, Dhall, G., additional, Gilles, F., additional, Ormandy, D., additional, Alston, R., additional, Estlin, E., additional, Gattamaneni, R., additional, Birch, J., additional, Kamaly-Asl, I., additional, Hemenway, M., additional, Rush, S., additional, Reginald, Y. A., additional, Nicolin, G., additional, Bartel, U., additional, Buncic, J. R., additional, Aguilera, D., additional, Flamini, R., additional, Mazewski, C., additional, Schniederjan, M., additional, Hayes, L., additional, Boydston, W., additional, MacDonald, T., additional, Fleming, A., additional, Jabado, N., additional, Saint-Martin, C., additional, Albrecht, S., additional, Ramsay, D. A., additional, Farmer, J. P., additional, Bendel, A., additional, Hansen, M., additional, Dugan, S., additional, and Mendelsohn, N., additional

Published
2012
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50. EPIDEMIOLOGY

Author

Khatua, S., primary, Brown, R., additional, Pearlman, M., additional, Vats, T., additional, Satge, D., additional, Stiller, C., additional, Rutkowski, S., additional, von Bueren, A. O., additional, Lacour, B., additional, Sommelet, D., additional, Nishi, M., additional, Massimino, M., additional, Garre, M.-L., additional, Moreno, F., additional, Hasle, H., additional, Jakab, Z., additional, Greenberg, M., additional, von der Weid, N., additional, Kuehni, C., additional, Zurriaga, O., additional, Vicente, M.-L., additional, Peris-Bonet, R., additional, Benesch, M., additional, Vekemans, M., additional, Sullivan, S., additional, Rickert, C., additional, Fisher, P. G., additional, Von Behren, J., additional, Nelson, D. O., additional, Reynolds, P., additional, Fukuoka, K., additional, Yanagisawa, T., additional, Suzuki, T., additional, Koga, T., additional, Wakiya, K., additional, Adachi, J.-i., additional, Mishima, K., additional, Fujimaki, T., additional, Matsutani, M., additional, Nishikawa, R., additional, Gidding, C., additional, Schieving, J., additional, Wesseling, P., additional, Ligtenberg, M., additional, Hoogerbrugge, N., additional, Jongmans, M., additional, Crosier, S., additional, Nicholson, S. L., additional, Robson, K., additional, Jacques, T., additional, Wharton, S., additional, Bown, N., additional, Michalski, A., additional, Pizer, B., additional, Clifford, S., additional, Sanden, E., additional, Visse, E., additional, Siesjo, P., additional, Darabi, A., additional, Nousome, D., additional, Lupo, P. J., additional, Scheurer, M. E., additional, Nulman, I., additional, Barrera, M., additional, Maxwell, C., additional, Koren, G., additional, Gorelyshev, S., additional, Matuev, K., additional, Lubnin, A., additional, Laskov, M., additional, Lemeneva, N., additional, Mazerkina, N., additional, Khuhlaeva, E., additional, Muller, K., additional, Bruns, F., additional, Pietsch, T., additional, Kortmann, R.-D., additional, Krishnatry, R., additional, Shirsat, N., additional, Kunder, R., additional, Epari, S., additional, Gupta, T., additional, Kurkure, P., additional, Vora, T., additional, Arora, B., additional, Moiyadi, A., additional, Jalali, R., additional, Swieszkowska, E., additional, Dembowska-Baginska, B., additional, Drogosiewicz, M., additional, Filipek, I., additional, Perek-Polnik, M., additional, Grajkowska, W., additional, Perek, D., additional, Johnston, D., additional, Cyr, J., additional, Strother, D., additional, Lafay-Cousin, L., additional, Fryer, C., additional, Scheinemann, K., additional, Carret, A.-S., additional, Fleming, A., additional, Larouche, V., additional, Bouffet, E., additional, Friedrich, C., additional, Gnekow, A. K., additional, Fleischhack, G., additional, Kramm, C. M., additional, Fruehwald, M. C., additional, Muller, H. L., additional, Calaminus, G., additional, Kordes, U., additional, Faldum, A., additional, Warmuth-Metz, M., additional, Kortmann, R. D., additional, Jung, I., additional, Kaatsch, P., additional, Caretti, V., additional, Bugiani, M., additional, Boor, I., additional, Schellen, P., additional, Vandertop, W. P., additional, Noske, D. P., additional, Kaspers, G., additional, Wurdinger, T., additional, Robinson, G., additional, Chingtagumpala, M., additional, Adesina, A., additional, Dalton, J., additional, Santi, M., additional, Sievert, A., additional, Wright, K., additional, Armstrong, G., additional, Boue, D., additional, Olshefski, R., additional, Scott, S., additional, Huang, A., additional, Cohn, R., additional, Gururangan, S., additional, Bowers, D., additional, Gilbertson, R., additional, Gajjar, A., additional, Ellison, D., additional, Chick, E., additional, Donson, A., additional, Owens, E., additional, Smith, A. A., additional, Madden, J. R., additional, Foreman, N. K., additional, Bakry, D., additional, Aronson, M., additional, Durno, C., additional, Hala, R., additional, Farah, R., additional, Amayiri, N., additional, Alharbi, Q., additional, Shamvil, A., additional, Ben-Shachar, S., additional, Constantini, S., additional, Rina, D., additional, Ellise, J., additional, Keiles, S., additional, Pollet, A., additional, Qaddoumi, I., additional, Gallinger, S., additional, Malkin, D., additional, Hawkins, C., additional, Tabori, U., additional, Trivedi, M., additional, Goodden, J., additional, Chumas, P., additional, Tyagi, A., additional, O'kane, R., additional, O'Kane, R., additional, Crimmins, D., additional, Picton, S., additional, and Elliott, M., additional

Published
2012
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