Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours

Nat Commun. 2015 Jan 22:6:5973. doi: 10.1038/ncomms6973.

Abstract

Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT, we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 12
  • Cisplatin / chemistry
  • Cohort Studies
  • DNA Mutational Analysis / methods*
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Exome*
  • Gene Dosage
  • Genes, Tumor Suppressor
  • Humans
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / surgery
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-kit / genetics
  • Seminoma / genetics
  • Spermatocytes / cytology
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / surgery

Substances

  • DNA-Binding Proteins
  • Interleukins
  • XRCC2 protein, human
  • interleukin-24
  • Proto-Oncogene Proteins c-kit
  • Cisplatin

Supplementary concepts

  • Testicular Germ Cell Tumor