Integrated molecular characterization of testicular germ cell tumors Journal Article

Authors: Shen, H.; Shih, J.; Hollern, D. P.; Wang, L.; Bowlby, R.; Tickoo, S. K.; Thorsson, V.; Mungall, A. J.; Newton, Y.; Hegde, A. M.; Armenia, J.; Sánchez-Vega, F.; Pluta, J.; Pyle, L. C.; Mehra, R.; Reuter, V. E.; Godoy, G.; Jones, J.; Shelley, C. S.; Feldman, D. R.; Vidal, D. O.; Lessel, D.; Kulis, T.; Cárcano, F. M.; Leraas, K. M.; Lichtenberg, T. M.; Brooks, D.; Cherniack, A. D.; Cho, J.; Heiman, D. I.; Kasaian, K.; Liu, M.; Noble, M. S.; Xi, L.; Zhang, H.; Zhou, W.; ZenKlusen, J. C.; Hutter, C. M.; Felau, I.; Zhang, J.; Schultz, N.; Getz, G.; Meyerson, M.; Stuart, J. M.; The Cancer Genome Atlas Research Network; Akbani, R.; Wheeler, D. A.; Laird, P. W.; Nathanson, K. L.; Nathanson, K. L.; Cortessis, V. K.; Hoadley, K. A.
Article Title: Integrated molecular characterization of testicular germ cell tumors
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. © 2018 The Author(s)
Keywords: dna methylation; kit; seminoma; nonseminoma; testicular germ cell tumors; copy number; the cancer genome atlas; exome sequencing; mir-375
Journal Title: Cell Reports
Volume: 23
Issue: 11
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2018-06-12
Start Page: 3392
End Page: 3406
Language: English
DOI: 10.1016/j.celrep.2018.05.039
PROVIDER: scopus
PUBMED: 29898407
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Satish K Tickoo
    369 Tickoo
  2. Darren Richard Feldman
    171 Feldman
  3. Victor Reuter
    901 Reuter
  4. Nikolaus D Schultz
    196 Schultz
  5. Joshua   Armenia
    22 Armenia
  6. Minwei Liu
    3 Liu