npj Precision Oncology (Nov 2024)

Driver mutations associated with signatures of platinum sensitivity in germ cell tumors

  • Yun Cheng Sawa,
  • Liwei Jia,
  • Harris Krause,
  • Margaret Meagher,
  • Frederick Millard,
  • Andrew Elliott,
  • John T. Lafin,
  • Christina Jamieson,
  • Emmanuel S. Antonarakis,
  • Anishka D’Souza,
  • Krinio Giannikou,
  • James F. Amatruda,
  • Siamak Daneshmand,
  • Rana R. McKay,
  • Matthew Oberley,
  • Chadi Nabhan,
  • Aditya Bagrodia

DOI
https://doi.org/10.1038/s41698-024-00727-2
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 6

Abstract

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Abstract We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance. Prevalence was calculated for platinum-resistant alterations (PRAs; KRAS, TP53, and KIT mutations, and MDM2 amplification) and high copy number amplifications (CNA ≥ 6 copies). Tumors were designated as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17). A transcriptomic signature associated with platinum sensitivity (PSS, high suggests increased sensitivity) was applied. KIT mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph. TP53 mutations were identified in 10% of primary GCTs versus 17% of met and 16.7% of lymph. MDM2 CNAs were similar between sites. PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.