Expanded detection of BAP1 alterations in cancer and tumor type-specific expression score comparison

• Published in: bioRxiv
• Main Authors: Sturgill, Ian R, Raab, Jesse R, Hoadley, Katherine A
• Format: Journal Article
• Language: English
• Published: United States 21.11.2023
• Subjects: genomic alteration; multiomics; gene expression profiling; BAP1; tumor suppressor gene
• ISSN: 2692-8205

is 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 of expression. 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 a local 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 were -altered, with alterations being predominantly CN-driven. Differential expression and survival analyses revealed both shared and tissue-specific consequences associated with alteration. Our findings broadly emphasize the improvements that are gained by using new computational approaches in large cancer-genome studies such as TCGA.