Expanded detection and impact of alterations in cancer.

Aberrant expression of the ( associated protein 1) tumor suppressor gene is a prominent risk factor for several tumor types and is important in tumor evolution and progression. Here we performed integrated multi-omics analyses using data from The Cancer Genome Atlas for 33 cancer types and over 10 000 individuals to identify alterations leading to disruption. We combined existing variant calls and new calls derived from a local realignment pipeline across multiple independent variant callers, increasing somatic variant detection by 41% from 182 to 257, including 11 indels ≥40 bp. The expanded detection of mutations highlights the power of new tools to uncover longer indels and impactful mutations. We developed an expression-based activity score and identified a transcriptional profile associated with disruption in cancer. has been proposed to play a critical role in controlling tumor plasticity and normal cell fate. Leveraging human and mouse liver datasets, loss in normal cells resulted in lower activity scores and lower scores were associated with a less-differentiated phenotype in embryonic cells. Together, our expanded mutant samples revealed a transcriptional signature in cancer cells, supporting 's influences on cellular plasticity and cell identity maintenance.