Association of genomic alterations with cisplatin resistance (cisR) in advanced germ cell tumors (aGCT)

4510 Background: 20% of patients (pts) with aGCT progress after initial chemotherapy (chemo), displaying at least partial cisR. We sought to characterize the genetic alterations in aGCT and identify markers of cisR. Methods: aGCT pts with available tumor tissue (except pure teratoma or malignant transformation) were eligible. Cisplatin sensitive (cisS) pts had a CR to chemo +/- surgery (if pathology = necrosis or teratoma) or PR + negative tumor markers lasting one year or more. CisR pts had non-teratoma GCT at post-chemo surgery or at relapse. Cis status was inevaluable (IE) if followup (f/u) was too short (without progression) or standard initial chemo was not given. Whole exome sequencing (WES) in 19 pts (10 cisR, 9 cisS) identified several mutations and copy number changes, which we confirmed by targeted exon-capture sequencing of 341 cancer-related genes (MSK-IMPACT). MSK-IMPACT was then preformed for 69 additional pts. Results on all 88 pts were analyzed for associations with clinicopathologic featu...