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2 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
Biomedical and Clinical Sciences, Neurosciences, Cancer Genomics, Genetics, Rare Diseases, Human Genome, Biotechnology, Precision Medicine, Brain Cancer, 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, 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. 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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