Integrated Molecular Characterization of Testicular Germ Cell Tumors

生殖细胞 生物 生殖细胞肿瘤 细菌 计算生物学 细胞生物学 癌症研究 遗传学 基因 化疗
作者
Hui Shen,Juliann Shih,Daniel P. Hollern,Linghua Wang,Reanne Bowlby,Satish K. Tickoo,Vésteinn Thórsson,Andrew J. Mungall,Yulia Newton,Apurva M. Hegde,Joshua Armenia,Francisco Sánchez-Vega,John Pluta,Louise C. Pyle,Rohit Mehra,Victor E. Reuter,Guilherme Godoy,Jeffrey Jones,Carl Simon Shelley,Darren R. Feldman,Daniel Onofre Vidal,Davor Lessel,Tomislav Kuliš,Flávio Mavignier Cárcano,Kristen Leraas,Tara M. Lichtenberg,Denise Brooks,Andrew D. Cherniack,Juok Cho,David I. Heiman,L. Sylvia,Minwei Liu,Michael S. Noble,Xi Liu,Hailei Zhang,Wanding Zhou,Jean C. Zenklusen,Carolyn M. Hutter,Ina Felau,Jiashan Zhang,Nikolaus Schultz,Gad Getz,Matthew Meyerson,Joshua M. Stuart,Rehan Akbani,David A. Wheeler,Peter W. Laird,Katherine L. Nathanson,Victoria K. Cortessis,Katherine A. Hoadley,Linghua Wang,Xi Liu,David A. Wheeler,Daniel Hughes,Kyle Covington,Joy C. Jayaseelan,Viktoriya Korchina,Lora Lewis,Hai Hu,HarshaVardhan Doddapaneni,Donna M. Muzny,Richard A. Gibbs,Katherine A. Hoadley,Daniel P. Hollern,Benjamin G. Vincent,Shengjie Chai,Christof C. Smith,J. Todd Auman,Yan Shi,Shaowu Meng,Tara Skelly,Donghui Tan,Umadevi Veluvolu,Piotr A. Mieczkowski,Corbin D. Jones,Matthew D. Wilkerson,Saianand Balu,Tom Bodenheimer,Alan P. Hoyle,Joshua M. Stuart,Lisle E. Mose,Janae V. Simons,Matthew G. Soloway,Jeffrey Roach,Joel S. Parker,D. Neil Hayes,Charles M. Perou,Juliann Shih,Andrew D. Cherniack,Matthew Meyerson,Gordon Saksena,Carrie Cibulskis,Steven E. Schumacher,Rameen Beroukhim,Stacey Gabriel,Reanne Bowlby,Andrew J. Mungall,Denise Brooks,L. Sylvia,Adrian Ally
出处
期刊:Cell Reports [Cell Press]
卷期号:23 (11): 3392-3406 被引量:362
标识
DOI:10.1016/j.celrep.2018.05.039
摘要

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.
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