Circulating tumor (ct)-DNA alterations in patients with testicular germ tumors.

Abstract

e16063 Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assay allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. To our knowledge, ctDNA genomic alterations observed in in testicular GCTs have not been heretofore described. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 31 Pts with testicular GCTs from multiple institutions in the United States that underwent ctDNA analysis using the Guardant360 platform were eligible. Two patients had one serial ctDNA sample. De-identified demographic data were collected in addition to data for ctDNA alterations. Guardant360 is a CLIA-certified ctDNA panel that assesses single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 31 patients with testicular GCTs, 162 ctDNA alterations were detected in 26 patients (84%) across 41 genes (Table). A median number of 3 alterations (range 1-19) was detected per sample. Among the 162 alterations, 88 were believed to be pathogenic and detectable in 20 patients (65%). 12/31 pts (39%) were documented to be post systemic therapy. The median age was 38 years (range 20-61). The most common pathogenic somatic alterations were KRAS (n = 12/88, 14%), CCND2 (n = 8/88, 9%), MET (n = 8/88, 9%), CDK6 (n = 7/88, 8%), TP53 (n = 6/88, 7%), and RAF1 (n = 5/88, 6%). In 2 patients with serial samples, 5 novel pathogenic alterations were detected in the second sample including FGFR2, APC, CDK6, RAF1, and MAPK1. Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to determine it's relevance in clinical practice. [Table: see text]