Genomic Features for Therapeutic Insights of Chemotherapy-Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart

Oncologist. 2019 Apr;24(4):e142-e145. doi: 10.1634/theoncologist.2018-0430. Epub 2019 Jan 18.


Primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, n = 22) and nonseminomatous (NS, n = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture-based technology (FoundationONE; Foundation Medicine, Inc., Cambridge, MA). Microsatellite instability (MSI) and tumor mutational burden (TMB, mutations [mut]/Mb) were determined.Statistically significant differences in genomic alterations (GA) of PMNSGCT versus NS included higher TP53 pathway GA (p < .0001), PIK3CA pathway GA (p < .0001), and lower cell-cycle pathway GA (p = .0004). There were no MSI-high PMNSGCT cases. Mean TMB was similar between the groups, but there were more ≥10 mut/Mb in the PMNSGCT group versus NS (11.4% vs. 4.6%).The GA identified in PMNSGCT were similar to the findings from NS, with differential opportunities for targeted therapies and immunotherapies. Further study of precision treatments appears warranted.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Genomics / methods*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mediastinal Neoplasms / genetics*
  • Mediastinal Neoplasms / pathology
  • Mutation*
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / secondary
  • Prognosis
  • Signal Transduction
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / secondary


  • Biomarkers, Tumor

Supplementary concepts

  • Nonseminomatous germ cell tumor
  • Testicular Germ Cell Tumor