Integrated Molecular Characterization of Testicular Germ Cell Tumors.

TitleIntegrated Molecular Characterization of Testicular Germ Cell Tumors.
Publication TypeJournal Article
Year of Publication2018
AuthorsShen, 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, Akbani, R, Wheeler, DA, Laird, PW, Nathanson, KL, Cortessis, VK, Hoadley, KA
Corporate Authors
JournalCell Rep
Volume23
Issue11
Pagination3392-3406
Date Published2018 Jun 12
ISSN2211-1247
Abstract

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.

DOI10.1016/j.celrep.2018.05.039
Alternate JournalCell Rep
PubMed ID29898407
Grant ListU24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States