Integrated Molecular Characterization of Testicular Germ Cell Tumors.

Cell Rep
Authors
Keywords
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.

Year of Publication
2018
Journal
Cell Rep
Volume
23
Issue
11
Pages
3392-3406
Date Published
2018 06 12
ISSN
2211-1247
DOI
10.1016/j.celrep.2018.05.039
PubMed ID
29898407
PubMed Central ID
PMC6075738
Links
Grant list
T32 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