W. Rathmell
Last active: 11/27/2019

Integrated Molecular Characterization of Testicular Germ Cell Tumors.

Shen H, Shih J, Hollern DP, Wang L, Bowlby R, Tickoo SK, Thorsson V, Mungall AJ, Newton Y, Hegde AM, Armenia J, Sánchez-Vega F, Pluta J, Pyle LC, Mehra R, Reuter VE, Godoy G, Jones J, Shelley CS, Feldman DR, Vidal DO, Lessel D, Kulis T, Cárcano FM, Leraas KM, Lichtenberg TM, Brooks D, Cherniack AD, Cho J, Heiman DI, Kasaian K, Liu M, Noble MS, Xi L, Zhang H, Zhou W, ZenKlusen JC, Hutter CM, Felau I, Zhang J, Schultz N, Getz G, Meyerson M, Stuart JM, Cancer Genome Atlas Research Network, Akbani R, Wheeler DA, Laird PW, Nathanson KL, Cortessis VK, Hoadley KA
Cell Rep. 2018 23 (11): 3392-3406

PMID: 29898407 · PMCID: PMC6075738 · DOI:10.1016/j.celrep.2018.05.039

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.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (11)

DNA Copy Number Variations DNA Methylation Gene Expression Regulation, Neoplastic Humans Male MicroRNAs Neoplasms, Germ Cell and Embryonal Proto-Oncogene Proteins c-kit ras Proteins Seminoma Testicular Neoplasms

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