Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup

被引:14
作者
da Silva, Luciane S. [1 ]
Mancano, Bruna M. [2 ,3 ]
de Paula, Flavia E. [3 ]
dos Reis, Mariana B. [1 ]
de Almeida, Gisele C. [4 ]
Matsushita, Marcus [4 ]
Junior, Carlos A. [5 ]
Evangelista, Adriane F. [1 ]
Saggioro, Fabiano [6 ]
Serafini, Luciano N. [6 ]
Stavale, Joao N. [7 ]
Malheiros, Suzana M. F. [7 ]
Lima, Matheus [8 ]
Hajj, Glaucia N. M. [8 ]
de Lima, Marcos A. [9 ]
Taylor, Michael D. [10 ,11 ]
Leal, Leticia F. [1 ]
Reis, Rui M. [1 ,12 ,13 ]
机构
[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil
[2] Barretos Canc Hosp, Children & Young Adults Canc Hosp, Sao Paulo, Brazil
[3] Barretos Canc Hosp, Mol Diagnost Lab, Sao Paulo, Brazil
[4] Barretos Canc Hosp, Dept Pathol, Sao Paulo, Brazil
[5] Barretos Canc Hosp, Dept Pediat Neurosurg, Sao Paulo, Brazil
[6] Univ Sao Paulo, Dept Pathol, Sao Paulo, Brazil
[7] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo, Brazil
[8] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, Brazil
[9] Barretos Canc Hosp, Stat Unit, Sao Paulo, Brazil
[10] Univ Toronto, Dept Surg, Toronto, ON, Canada
[11] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[12] Univ Minho, Life & Hlth Sci Res Inst, Sch Med, Braga, Portugal
[13] 3Bs PT Govt Associate Lab, Life & Hlth Sci Res Inst, Braga, Portugal
关键词
MOLECULAR SUBGROUPS; OUTCOME PREDICTION; TUMOR-SUPPRESSOR; LANDSCAPE; CLASSIFICATION; G-ALPHA(S); MYCN;
D O I
10.1016/j.jmoldx.2020.04.207
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MBSHH, MBWNT, MBGRP3, or MBGRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MBSHH (47.7%), MBWNT (1.6.1%), MBGRP3 (15.4%), and MBGRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MBSHH. TP53, MYCN, SOX2, and MET were also up-regulated in MBSHH, whereas PTEN was upregulated in MBGRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MBSHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MBSHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MBSHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs.
引用
收藏
页码:957 / 966
页数:10
相关论文
共 44 条
[31]   Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study [J].
Schwalbe, Edward C. ;
Lindsey, Janet C. ;
Nakjang, Sirintra ;
Crosier, Stephen ;
Smith, Amanda J. ;
Hicks, Debbie ;
Rafiee, Gholamreza ;
Hill, Rebecca M. ;
Iliasova, Alice ;
Stone, Thomas ;
Pizer, Barry ;
Michalski, Antony ;
Joshi, Abhijit ;
Wharton, Stephen B. ;
Jacques, Thomas S. ;
Bailey, Simon ;
Williamson, Daniel ;
Clifford, Steven C. .
LANCET ONCOLOGY, 2017, 18 (07) :958-971
[32]   Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes [J].
Sharma, Tanvi ;
Schwalbe, Edward C. ;
Williamson, Daniel ;
Sill, Martin ;
Hovestadt, Volker ;
Mynarek, Martin ;
Rutkowski, Stefan ;
Robinson, Giles W. ;
Gajjar, Amar ;
Cavalli, Florence ;
Ramaswamy, Vijay ;
Taylor, Michael D. ;
Lindsey, Janet C. ;
Hill, Rebecca M. ;
Jaeger, Natalie ;
Korshunov, Andrey ;
Hicks, Debbie ;
Bailey, Simon ;
Kool, Marcel ;
Chavez, Lukas ;
Northcott, Paul A. ;
Pfister, Stefan M. ;
Clifford, Steven C. .
ACTA NEUROPATHOLOGICA, 2019, 138 (02) :309-326
[33]   Genetic and molecular alterations across medulloblastoma subgroups [J].
Skowron, Patryk ;
Ramaswamy, Vijay ;
Taylor, Michael D. .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2015, 93 (10) :1075-1084
[34]   Pleiotropic role for MYCN in medulloblastoma [J].
Swartling, Fredrik J. ;
Grimmer, Matthew R. ;
Hackett, Christopher S. ;
Northcott, Paul A. ;
Fan, Qi-Wen ;
Goldenberg, David D. ;
Lau, Jasmine ;
Masic, Selma ;
Nguyen, Kim ;
Yakovenko, Slava ;
Zhe, Xiao-Ning ;
Gilmer, Heather C. Flynn ;
Collins, Rodney ;
Nagaoka, Mai ;
Phillips, Joanna J. ;
Jenkins, Robert B. ;
Tihan, Tarik ;
Vandenberg, Scott R. ;
James, C. David ;
Tanaka, Kohichi ;
Taylor, Michael D. ;
Weiss, William A. ;
Chesler, Louis .
GENES & DEVELOPMENT, 2010, 24 (10) :1059-1072
[35]   Molecular subgroups of medulloblastoma: the current consensus [J].
Taylor, Michael D. ;
Northcott, Paul A. ;
Korshunov, Andrey ;
Remke, Marc ;
Cho, Yoon-Jae ;
Clifford, Steven C. ;
Eberhart, Charles G. ;
Parsons, D. Williams ;
Rutkowski, Stefan ;
Gajjar, Amar ;
Ellison, David W. ;
Lichter, Peter ;
Gilbertson, Richard J. ;
Pomeroy, Scott L. ;
Kool, Marcel ;
Pfister, Stefan M. .
ACTA NEUROPATHOLOGICA, 2012, 123 (04) :465-472
[36]   The clinical importance of medulloblastoma extent of resection: a systematic review [J].
Thompson, Eric M. ;
Bramall, Alexa ;
Herndon, James E. ;
Taylor, Michael D. ;
Ramaswamy, Vijay .
JOURNAL OF NEURO-ONCOLOGY, 2018, 139 (03) :523-539
[37]   Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis [J].
Thompson, Eric M. ;
Hielscher, Thomas ;
Bouffet, Eric ;
Remke, Marc ;
Luu, Betty ;
Gururangan, Sridharan ;
McLendon, Roger E. ;
Bigner, Darell D. ;
Lipp, Eric S. ;
Perreault, Sebastien ;
Cho, Yoon-Jae ;
Grant, Gerald ;
Kim, Seung-Ki ;
Lee, Ji Yeoun ;
Rao, Amulya A. Nageswara ;
Giannini, Caterina ;
Li, Kay Ka Wai ;
Ng, Ho-Keung ;
Yao, Yu ;
Kumabe, Toshihiro ;
Tominaga, Teiji ;
Grajkowska, Wieslawa A. ;
Perek-Polnik, Marta ;
Low, David C. Y. ;
Seow, Wan Tew ;
Chang, Kenneth T. E. ;
Mora, Jaume ;
Pollack, Ian F. ;
Hamilton, Ronald L. ;
Leary, Sarah ;
Moore, Andrew S. ;
Ingram, Wendy J. ;
Hallahan, Andrew R. ;
Jouvet, Anne ;
Fevre-Montange, Michelle ;
Vasiljevic, Alexandre ;
Faure-Conter, Cecile ;
Shofuda, Tomoko ;
Kagawa, Naoki ;
Hashimoto, Naoya ;
Jabado, Nada ;
Weil, Alexander G. ;
Gayden, Tenzin ;
Wataya, Takafumi ;
Shalaby, Tarek ;
Grotzer, Michael ;
Zitterbart, Karel ;
Sterba, Jaroslav ;
Kren, Leos ;
Hortobagyi, Tibor .
LANCET ONCOLOGY, 2016, 17 (04) :484-495
[38]   Genornics identifies medulloblastoma subgroups that are enriched for specific genetic alterations [J].
Thompson, MC ;
Fuller, C ;
Hogg, TL ;
Dalton, J ;
Finkelstein, D ;
Lau, CC ;
Chintagumpala, M ;
Adesina, A ;
Ashley, DM ;
Kellie, SJ ;
Michael, DT ;
Curran, T ;
Gajjar, A ;
Gilbertson, RJ .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (12) :1924-1931
[39]   Diagnosis of multiple cancer types by shrunken centroids of gene expression [J].
Tibshirani, R ;
Hastie, T ;
Narasimhan, B ;
Chu, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :6567-6572
[40]  
van der Maaten L, 2014, J MACH LEARN RES, V15, P3221