Integrated Molecular Characterization of Testicular Germ Cell Tumors

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

45 Citations (Scopus)

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. 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 (US)
Pages (from-to)3392-3406
Number of pages15
JournalCell Reports
Volume23
Issue number11
DOIs
StatePublished - Jun 12 2018

Fingerprint

Seminoma
Tumors
Cells
Embryonal Carcinoma
Mutation
Teratoma
MicroRNAs
Epigenomics
Biomarkers
Endodermal Sinus Tumor
Molecular Pathology
Aneuploidy
DNA Methylation
Proteomics
Methylation
Histology
Infiltration
Testicular Germ Cell Tumor
Assays
DNA

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Integrated Molecular Characterization of Testicular Germ Cell Tumors. / The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 23, No. 11, 12.06.2018, p. 3392-3406.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network 2018, 'Integrated Molecular Characterization of Testicular Germ Cell Tumors', Cell Reports, vol. 23, no. 11, pp. 3392-3406. https://doi.org/10.1016/j.celrep.2018.05.039
The Cancer Genome Atlas Research Network. / Integrated Molecular Characterization of Testicular Germ Cell Tumors. In: Cell Reports. 2018 ; Vol. 23, No. 11. pp. 3392-3406.
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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. 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.",
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AU - Reuter, Victor E.

AU - Godoy, Guilherme

AU - Jones, Jeffrey

AU - Shelley, Carl S.

AU - Feldman, Darren R.

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AU - Leraas, Kristen M.

AU - Lichtenberg, Tara M.

AU - Brooks, Denise

AU - Cherniack, Andrew D.

AU - Cho, Juok

AU - Heiman, David I.

AU - Kasaian, Katayoon

AU - Liu, Minwei

AU - Noble, Michael S.

AU - Xi, Liu

AU - Zhang, Hailei

AU - Zhou, Wanding

AU - ZenKlusen, Jean C.

AU - Hutter, Carolyn M.

AU - Felau, Ina

AU - Zhang, Jiashan

AU - Schultz, Nikolaus

AU - Getz, Gad

AU - Meyerson, Matthew

AU - Stuart, Joshua M.

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KW - DNA methylation

KW - exome sequencing

KW - KIT

KW - miR-375

KW - nonseminoma

KW - seminoma

KW - testicular germ cell tumors

KW - The Cancer Genome Atlas

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