Expanded detection ofBAP1alterations in cancer and tumor type-specific expression score comparison

Abstract

AbstractBAP1is a tumor suppressor gene that was originally studied in uveal melanoma (UVM), kidney renal cell clear cell carcinoma (KIRC), and malignant mesothelioma (MESO). Early analyses focused on single-nucleotide variants, but other alteration types such as larger indels and gene-level copy number (CN) loss can also lead to loss ofBAP1expression. We performed integrated multi-omic analyses using data from The Cancer Genome Atlas (TCGA) for 33 cancer types and more than 10,000 individuals. We combined and manually reviewed existing variant calls and new calls derived from ade novolocal realignment pipeline across multiple independent variant callers including indel callers, increasing detection of high-quality somatic variant calls by 30% from 91 to 130, including 7 indels ≥40bp. Including CN loss alterations, 1561 samples from 32 cancer types wereBAP1-altered, with alterations being predominantly CN-driven. Differential expression and survival analyses revealed both shared and tissue-specific consequences associated withBAP1alteration. Our findings broadly emphasize the improvements that are gained by using new computational approaches in large cancer-genome studies such as TCGA.