Germline-somatic liaison dictates cancer subtype via de novo steroid biosynthesis
This study investigates the cooperation between germline genetic variants and somatic mutations in prostate cancer. Specifically, we dissected the interplay between a germline variant at the 7p14.3 locus (rs1376350, G>A) and early recurrent prostate cancer-specific mutation in the Speckle-Type POZ protein (SPOP) gene across human prostate adenocarcinomas. The transcriptomes of multiple edited models pointed to Gli3 and the Hedgehog signaling pathway in a genotype-specific manner. Overall design: RNA-seq profiling of PC3 and LnCaP cellines with single-nucleotide, macrodeletion, microdeletion, and distruption of binging motifs at genomic site 7p14.3 (rs1376350)