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 AuthorsCancer Genome Atlas Research Network
JournalCell Rep
Volume23
Issue11
Pagination3392-3406
Date Published2018 06 12
ISSN2211-1247
KeywordsDNA 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
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
PubMed Central IDPMC6075738
Grant ListT32 GM008638 / GM / NIGMS NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
KL2 TR001879 / TR / NCATS NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
R01 CA180778 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
P30 ES013508 / ES / NIEHS NIH HHS / United States
U24 CA210988 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States