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Cytogenetic prognostication within medulloblastoma subgroups

Shih, David J. H. and Northcott, Paul A. and Remke, Marc and Korshunov, Andrey and Ramaswamy, Vijay and Garami, Miklós and Hauser, Peter and Bognár, László and Klekner, Álmos (2014) Cytogenetic prognostication within medulloblastoma subgroups. Journal of Clinical Oncology, 32 (9). pp. 886-896. ISSN 1527-7755

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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.

Item Type: Article
Additional Information: Teljes szerzőség: Shih, David J. H. és Northcott, Paul A. és Remke, Marc és Korshunov, Andrey és Ramaswamy, Vijay és Kool, Marcel és Luu, Betty és Yao, Yuan és Wang, Xin és Dubuc, Adrian M. és Garzia, Livia és Peacock, John és Mack, Stephen C. és Wu, Xiaochong és Rolider, Adi és Morrissy, A Sorana és Cavalli, Florence M. G. és Jones, David T. W. és Zitterbart, Karel és Faria, Claudia C. és Schüller, Ulrich és Kren, Leos és Kumabe, Toshihiro és Tominaga, Teiji és Shin Ra, Young és Garami, Miklós és Hauser, Peter és Chan, Jennifer A. és Robinson, Shenandoah és Bognár, László és Klekner, Álmos és Saad, Ali G. és Liau, Linda M. és Albrecht, Steffen és Fontebasso, Adam és Cinalli, Giuseppe és De Antonellis, Pasqualino és Zollo, Massimo és Cooper, Michael K. és Thompson, Reid C. és Bailey, Simon és Lindsey, Janet C. és Di Rocco, Concezio és Massimi, Luca és Michiels, Erna M. C. és Scherer, Stephen W. és Phillips, Joanna J. és Gupta, Nalin és Fan, Xing és Muraszko, Karin M. és Vibhakar, Rajeev és Eberhart, Charles G. és Fouladi, Maryam és Lach, Boleslaw és Jung, Shin és Wechsler-Reya, Robert J. és Fèvre-Montange, Michelle és Jouvet, Anne és Jabado, Nada és Pollack, Ian F. és Weiss, William A. és Lee, Ji-Yeoun és Cho, Byung-Kyu és Kim, Seung-Ki és Wang, Kyu-Chang és Leonard, Jeffrey R. és Rubin, Joshua B. és De Torres, Carmen és Lavarino, Cinzia és Mora, Jaume és Cho, Yoon-Jae és Tabori, Uri és Olson, James M. és Gajjar, Amar és Packer, Roger J. és Rutkowski, Stefan és Pomeroy, Scott L. és French, Pim J. és Kloosterhof, Nanne K. és Kros, Johan M. és Van Meir, Erwin G. és Clifford, Steven C. és Bourdeaut, Franck és Delattre, Olivier és Doz, François F. és Hawkins, Cynthia E. és Malkin, David és Grajkowska, Wieslawa A. és Perek-Polnik, Marta és Bouffet, Eric és Rutka, James T. és Pfister, Stefan M. és Taylor, Michael D.
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
Depositing User: Dr. Álmos Klekner
Date Deposited: 17 Nov 2014 07:42
Last Modified: 01 Apr 2016 23:15
URI: http://real.mtak.hu/id/eprint/15784

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