Genomic Characterization of Testicular Germ Cell Tumors Relapsing After Chemotherapy.

European Urology Focus
Andrea NecchiJeffrey S Ross

Abstract

Although both seminomatous and nonseminomatous testicular germ cell tumors (TGCTs) have favorable outcomes with chemotherapy, a subset is chemorefractory, and novel therapeutic options are needed. To molecularly characterize chemotherapy-refractory TGCTs. Archival tissues from 107 chemotherapy-treated and relapsed TGCT patients (23 seminomas; 84 nonseminomas) underwent hybrid-capture-based genomic profiling to evaluate four classes of genomic alterations (GAs). Tumor mutational burden (TMB) and microsatellite instability (MSI) were also measured. Genomic profiling on tumor samples from chemotherapy-refractory TGCTs. Descriptive analyses and differences between seminoma and nonseminoma subgroups were reported. The mean GA/tumor was 2.9 for seminomas and 4.0 for nonseminomas (p=0.04). KRAS alterations (mainly amplifications) were the most common GAs at the single-gene level (47.8% of seminomas and 51.2% of nonseminomas). RAS-RAF pathway (56.5% vs 52.3%) and cell-cycle pathway (52.2% vs 56.0%) were the most common GA classes in seminomas and nonseminomas, respectively. Receptor tyrosine kinase pathway and PI3K pathway GAs were more frequent in seminomas (p=0.02). Median TMB was 1.8 mutations/Mb for seminomas and 2.7 mutations/Mb f...Continue Reading

Citations

Mar 9, 2019·Expert Opinion on Pharmacotherapy·Winfried AlsdorfChristoph Oing
Oct 14, 2020·Nature Reviews. Urology·Filippo PederzoliAndrea Necchi
Apr 4, 2021·International Journal of Molecular Sciences·João LoboRui Henrique
Jul 18, 2021·International Journal of Clinical Oncology·Giulio FrancoliniStefano Arcangeli
Jul 29, 2021·Cancer Letters·Margaretha A SkowronDaniel Nettersheim
Dec 7, 2021·Pediatric Blood & Cancer·Adeline YangDinesh Rakheja

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