Low-copy piggyBac transposon mutagenesis in mice identifies genes driving melanoma.

ABSTRACT: Despite considerable efforts to sequence hypermutated cancers such as melanoma, distinguishing cancer-driving genes from thousands of recurrently mutated genes remains a significant challenge. To circumvent the problematic background mutation rates and identify new melanoma driver genes, we carried out a low-copy piggyBac transposon mutagenesis screen in mice. We induced eleven melanomas with mutation burdens that were 100-fold lower relative to human melanomas. Thirty-eight implicated genes, including two known drivers of human melanoma, were classified into three groups based on high, low, or background-level mutation frequencies in human melanomas, and we further explored the functional significance of genes in each group. For two genes overlooked by prevailing discovery methods, we fou

SUBMITTER: Ni TK 

PROVIDER: S-EPMC3780872 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature