Integrated Molecular Characterization of Testicular Germ Cell Tumors

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticlepeer-review

301 Scopus citations


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. Shen et al. identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting.

Original languageEnglish
Pages (from-to)3392-3406
Number of pages15
JournalCell Reports
Issue number11
StatePublished - 12 Jun 2018


  • DNA methylation
  • KIT
  • The Cancer Genome Atlas
  • copy number
  • exome sequencing
  • miR-375
  • nonseminoma
  • seminoma
  • testicular germ cell tumors


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