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12 results on '"Emery, Lyndsey"'

1. Heterogeneity within the PF-EPN-B ependymoma subgroup

Author

Cavalli, Florence MG, Hübner, Jens-Martin, Sharma, Tanvi, Luu, Betty, Sill, Martin, Zapotocky, Michal, Mack, Stephen C, Witt, Hendrik, Lin, Tong, Shih, David JH, Ho, Ben, Santi, Mariarita, Emery, Lyndsey, Hukin, Juliette, Dunham, Christopher, McLendon, Roger E, Lipp, Eric S, Gururangan, Sridharan, Grossbach, Andrew, French, Pim, Kros, Johan M, van Veelen, Marie-Lise C, Rao, Amulya A Nageswara, Giannini, Caterina, Leary, Sarah, Jung, Shin, Faria, Claudia C, Mora, Jaume, Schüller, Ulrich, Alonso, Marta M, Chan, Jennifer A, Klekner, Almos, Chambless, Lola B, Hwang, Eugene I, Massimino, Maura, Eberhart, Charles G, Karajannis, Matthias A, Lu, Benjamin, Liau, Linda M, Zollo, Massimo, Ferrucci, Veronica, Carlotti, Carlos, Tirapelli, Daniela PC, Tabori, Uri, Bouffet, Eric, Ryzhova, Marina, Ellison, David W, Merchant, Thomas E, Gilbert, Mark R, Armstrong, Terri S, Korshunov, Andrey, Pfister, Stefan M, Taylor, Michael D, Aldape, Kenneth, Pajtler, Kristian W, Kool, Marcel, and Ramaswamy, Vijay

Subjects
Genetics, Cancer, Clinical Research, Rare Diseases, Human Genome, Brain Cancer, Brain Disorders, Adolescent, Adult, Age Factors, Child, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Ependymoma, Female, Gene Expression Profiling, Humans, Infratentorial Neoplasms, Kaplan-Meier Estimate, Male, Microarray Analysis, Middle Aged, Young Adult, Posterior fossa, Subgrouping, PFB, PFA, Clustering, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Published
2018

2. BRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers

Author

Maxwell, Kara N, Wubbenhorst, Bradley, Wenz, Brandon M, De Sloover, Daniel, Pluta, John, Emery, Lyndsey, Barrett, Amanda, Kraya, Adam A, Anastopoulos, Ioannis N, Yu, Shun, Jiang, Yuchao, Chen, Hao, Zhang, Nancy R, Hackman, Nicole, D’Andrea, Kurt, Daber, Robert, Morrissette, Jennifer JD, Mitra, Nandita, Feldman, Michael, Domchek, Susan M, and Nathanson, Katherine L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Rare Diseases, Breast Cancer, Ovarian Cancer, Cancer, Adult, Aged, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Methylation, Female, Germ-Line Mutation, Humans, Kaplan-Meier Estimate, Loss of Heterozygosity, Middle Aged, Outcome Assessment, Health Care, Ovarian Neoplasms, Promoter Regions, Genetic, Proportional Hazards Models
Abstract

Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond. Herein we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors. Retention of the normal BRCA1 or BRCA2 allele (absence of locus-specific loss of heterozygosity (LOH)) is observed in 7% of BRCA1 ovarian, 16% of BRCA2 ovarian, 10% of BRCA1 breast, and 46% of BRCA2 breast tumors. These tumors have equivalent homologous recombination deficiency scores to sporadic tumors, significantly lower than scores in tumors with locus-specific LOH (ovarian, P = 0.0004; breast P

Published
2017

3. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Author

Ramaswamy, Vijay, Hielscher, Thomas, Mack, Stephen C, Lassaletta, Alvaro, Lin, Tong, Pajtler, Kristian W, Jones, David TW, Luu, Betty, Cavalli, Florence MG, Aldape, Kenneth, Remke, Marc, Mynarek, Martin, Rutkowski, Stefan, Gururangan, Sridharan, McLendon, Roger E, Lipp, Eric S, Dunham, Christopher, Hukin, Juliette, Eisenstat, David D, Fulton, Dorcas, van Landeghem, Frank KH, Santi, Mariarita, van Veelen, Marie-Lise C, Van Meir, Erwin G, Osuka, Satoru, Fan, Xing, Muraszko, Karin M, Tirapelli, Daniela PC, Oba-Shinjo, Sueli M, Marie, Suely KN, Carlotti, Carlos G, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Faria, Claudia C, Nunes, Sofia, Mora, Jaume, Hamilton, Ronald L, Hauser, Peter, Jabado, Nada, Petrecca, Kevin, Jung, Shin, Massimi, Luca, Zollo, Massimo, Cinalli, Giuseppe, Bognár, László, Klekner, Almos, Hortobágyi, Tibor, Leary, Sarah, Ermoian, Ralph P, Olson, James M, Leonard, Jeffrey R, Gardner, Corrine, Grajkowska, Wieslawa A, Chambless, Lola B, Cain, Jason, Eberhart, Charles G, Ahsan, Sama, Massimino, Maura, Giangaspero, Felice, Buttarelli, Francesca R, Packer, Roger J, Emery, Lyndsey, Yong, William H, Soto, Horacio, Liau, Linda M, Everson, Richard, Grossbach, Andrew, Shalaby, Tarek, Grotzer, Michael, Karajannis, Matthias A, Zagzag, David, Wheeler, Helen, von Hoff, Katja, Alonso, Marta M, Tuñon, Teresa, Schüller, Ulrich, Zitterbart, Karel, Sterba, Jaroslav, Chan, Jennifer A, Guzman, Miguel, Elbabaa, Samer K, Colman, Howard, Dhall, Girish, Fisher, Paul G, Fouladi, Maryam, Gajjar, Amar, Goldman, Stewart, Hwang, Eugene, Kool, Marcel, Ladha, Harshad, Vera-Bolanos, Elizabeth, Wani, Khalida, Lieberman, Frank, Mikkelsen, Tom, Omuro, Antonio M, Pollack, Ian F, Prados, Michael, Robins, H Ian, and Soffietti, Riccardo

Subjects
Humans, Ependymoma, Infratentorial Neoplasms, Combined Modality Therapy, Retrospective Studies, Cohort Studies, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Cytoreduction Surgical Procedures, Rare Diseases, Pediatric Cancer, Cancer, Pediatric, Patient Safety, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

4. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma

Author

Linette, Gerald P., Stadtmauer, Edward A., Maus, Marcela V., Rapoport, Aaron P., Levine, Bruce L., Emery, Lyndsey, Litzky, Leslie, Bagg, Adam, Carreno, Beatriz M., Cimino, Patrick J., Binder-Scholl, Gwendolyn K., Smethurst, Dominic P., Gerry, Andrew B., Pumphrey, Nick J., Bennett, Alan D., Brewer, Joanna E., Dukes, Joseph, Harper, Jane, Tayton-Martin, Helen K., Jakobsen, Bent K., Hassan, Namir J., Kalos, Michael, and June, Carl H.

Published
2013
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5. Abstract 2990: Evidence for diverse mechanisms of tumorigenesis in breast and ovarian tumors of BRCA1/2 carriers

Author

Maxwell, Kara N., primary, De Sloover, Daniel, additional, Wubbenhorst, Bradley, additional, Wenz, Brandon, additional, Lunceford, Nicole, additional, Emery, Lyndsey, additional, D'Andrea, Kurt, additional, Daber, Robert D., additional, Feldman, Michael D., additional, Domchek, Susan M., additional, and Nathanson, Katherine L., additional

Published
2015
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8. The mutational spectrum of breast and ovarian tumors from BRCA1 and BRCA2 mutation carriers.

Author

Maxwell, Kara Noelle, primary, De Sloover, Daniel, additional, Emery, Lyndsey, additional, Wubbenhorst, Bradley, additional, D'Andrea, Kurt P, additional, Long, Jessica, additional, Mueller, Rebecca, additional, Powers, Jacqueline, additional, Stopfer, Jill, additional, Feldman, Michael D, additional, Domchek, Susan M., additional, Daber, Robert, additional, and Nathanson, Katherine L., additional

Published
2013
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10. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Author

Cain, Jason, Ahsan, Sama, Van Meir, Erwin G., Guzman, Miguel, Rao, Amulya A. Nageswara, Tabori, Uri, Giannini, Caterina, Metellus, Phillipe, Soto, Horacio, Dirks, Peter, Wheeler, Helen, Colman, Howard, Merchant, Thomas E., Pfister, Stefan M., Kool, Marcel, Soffietti, Riccardo, Alonso, Marta M., Fouladi, Maryam, Giangaspero, Felice, Oba-Shinjo, Sueli M., Ramaswamy, Vijay, Shalaby, Tarek, Faria, Claudia C., Bartels, Ute, Hortobágyi, Tibor, Tirapelli, Daniela P.C., Yong, William H., Pajtler, Kristian W., Chambless, Lola B., Korshunov, Andrey, Wani, Khalida, Luu, Betty, Lassaletta, Alvaro, Massimi, Luca, Lin, Tong, Vera-Bolanos, Elizabeth, Goldman, Stewart, Dhall, Girish, Ladha, Harshad, Massimino, Maura, Liau, Linda M., Fan, Xing, Ellison, David W., Jones, David T.W., Aldape, Kenneth, McLendon, Roger E., Emery, Lyndsey, Chan, Jennifer A., Gardner, Corrine, Olson, James M., Gururangan, Sridharan, Fulton, Dorcas, Zagzag, David, Hamilton, Ronald L., Robins, H. Ian, Grossbach, Andrew, Eisenstat, David D., Omuro, Antonio M., Lipp, Eric S., Packer, Roger J., Gilbert, Mark R., Schüller, Ulrich, Zitterbart, Karel, Jung, Shin, Tuñon, Teresa, Dunham, Christopher, Mack, Stephen C., Cavalli, Florence M.G., Mynarek, Martin, Ermoian, Ralph P., Leary, Sarah, Hawkins, Cynthia E., Armstrong, Terri S., Osuka, Satoru, Carlotti, Carlos G., Klekner, Almos, Leonard, Jeffrey R., Hauser, Peter, Zollo, Massimo, Marie, Suely K.N., Van Veelen, Marie-Lise C., Bouffet, Eric, Rutka, James T., Sterba, Jaroslav, Mora, Jaume, Grotzer, Michael, Fisher, Paul G., Cinalli, Giuseppe, Nunes, Sofia, Lieberman, Frank, Hukin, Juliette, Everson, Richard, Pollack, Ian F., Grajkowska, Wieslawa A., Santi, Mariarita, Lee, Ji Yeoun, Elbabaa, Samer K., Taylor, Michael D., Remke, Marc, Mikkelsen, Tom, Van Landeghem, Frank K.H., Karajannis, Matthias A., Hwang, Eugene, Rutkowski, Stefan, Von Hoff, Katja, Eberhart, Charles G., Muraszko, Karin M., Prados, Michael, Bognár, László, Jabado, Nada, Gajjar, Amar, Buttarelli, Francesca R., Hielscher, Thomas, Wu, Jing, and Petrecca, Kevin

Subjects
10. No inequality, 3. Good health
Abstract

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.

11. Heterogeneity within the PF-EPN-B ependymoma subgroup

Author

Almos Klekner, David W. Ellison, Vijay Ramaswamy, Betty Luu, Marcel Kool, David Shih, Eugene Hwang, Andrey Korshunov, Mariarita Santi, Michal Zapotocky, Juliette Hukin, Marta M. Alonso, Hendrik Witt, Caterina Giannini, Stephen C. Mack, Thomas E. Merchant, Tanvi Sharma, Ulrich Schüller, Marie Lise C. van Veelen, Jennifer A. Chan, Kristian W. Pajtler, Martin Sill, Christopher Dunham, Amulya A. Nageswara Rao, Benjamin Y. Lu, Maura Massimino, Sarah Leary, Daniela Pretti da Cunha Tirapelli, Eric S. Lipp, Tong Lin, Andrew J. Grossbach, Massimo Zollo, Carlos Gilberto Carlotti, Eric Bouffet, Matthias A. Karajannis, Terri S. Armstrong, Jaume Mora, Jens Martin Hübner, Ben Ho, Charles G. Eberhart, Lola B. Chambless, Roger E. McLendon, Veronica Ferrucci, Linda M. Liau, Kenneth Aldape, Florence M.G. Cavalli, Claudia C. Faria, Stefan M. Pfister, Sridharan Gururangan, Shin Jung, Pim J. French, Michael D. Taylor, Uri Tabori, Lyndsey Emery, Marina Ryzhova, Johan M. Kros, Mark R. Gilbert, Cavalli F.M.G., Hubner J.-M., Sharma T., Luu B., Sill M., Zapotocky M., Mack S.C., Witt H., Lin T., Shih D.J.H., Ho B., Santi M., Emery L., Hukin J., Dunham C., McLendon R.E., Lipp E.S., Gururangan S., Grossbach A., French P., Kros J.M., van Veelen M.-L.C., Rao A.A.N., Giannini C., Leary S., Jung S., Faria C.C., Mora J., Schuller U., Alonso M.M., Chan J.A., Klekner A., Chambless L.B., Hwang E.I., Massimino M., Eberhart C.G., Karajannis M.A., Lu B., Liau L.M., Zollo M., Ferrucci V., Carlotti C., Tirapelli D.P.C., Tabori U., Bouffet E., Ryzhova M., Ellison D.W., Merchant T.E., Gilbert M.R., Armstrong T.S., Korshunov A., Pfister S.M., Taylor M.D., Aldape K., Pajtler K.W., Kool M., Ramaswamy V., Neurology, Pathology, Neurosurgery, Cavalli, Florence M. G., Hübner, Jens-Martin, Sharma, Tanvi, Luu, Betty, Sill, Martin, Zapotocky, Michal, Mack, Stephen C., Witt, Hendrik, Lin, Tong, Shih, David J. H., Ho, Ben, Santi, Mariarita, Emery, Lyndsey, Hukin, Juliette, Dunham, Christopher, Mclendon, Roger E., Lipp, Eric S., Gururangan, Sridharan, Grossbach, Andrew, French, Pim, Kros, Johan M., van Veelen, Marie-Lise C., Rao, Amulya A. Nageswara, Giannini, Caterina, Leary, Sarah, Jung, Shin, Faria, Claudia C., Mora, Jaume, Schüller, Ulrich, Alonso, Marta M., Chan, Jennifer A., Klekner, Almo, Chambless, Lola B., Hwang, Eugene I., Massimino, Maura, Eberhart, Charles G., Karajannis, Matthias A., Lu, Benjamin, Liau, Linda M., Zollo, Massimo, Ferrucci, Veronica, Carlotti, Carlo, Tirapelli, Daniela P. C., Tabori, Uri, Bouffet, Eric, Ryzhova, Marina, Ellison, David W., Merchant, Thomas E., Gilbert, Mark R., Armstrong, Terri S., Korshunov, Andrey, Pfister, Stefan M., Taylor, Michael D., Aldape, Kenneth, Pajtler, Kristian W., Kool, Marcel, and Ramaswamy, Vijay

Subjects
Oncology, Ependymoma, Male, PFA, Posterior fossa, PFB, Infratentorial Neoplasms, Kaplan-Meier Estimate, Subgrouping, Cohort Studies, 0302 clinical medicine, Age Factor, Young adult, Child, Cancer, DNA Copy Number Variation, Infratentorial Neoplasm, Age Factors, Methylation, Orvostudományok, Middle Aged, Subependymoma, 030220 oncology & carcinogenesis, DNA methylation, Female, Human, Adult, medicine.medical_specialty, DNA Copy Number Variations, Adolescent, CITOGENÉTICA, Clinical Sciences, Biology, Klinikai orvostudományok, Article, Clustering, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Rare Diseases, Clinical Research, Internal medicine, Genetics, medicine, Humans, Microarray Analysi, Neurology & Neurosurgery, Microarray analysis techniques, Gene Expression Profiling, Human Genome, Neurosciences, DNA Methylation, Microarray Analysis, medicine.disease, Brain Disorders, Brain Cancer, Gene expression profiling, Neurology (clinical), Cohort Studie, 030217 neurology & neurosurgery
Abstract

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Published
2018

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