Pervasiveness of HLA allele-specific expression loss across tumor types.

Background: Efficient presentation of mutant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune-mediated killing of cancer cells. According to recent reports, patient HLA-I genotypes can impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has also been reported in different tumor types, the role of HLA-I allele-specific expression loss - that is, the preferential RNA expression loss of specific HLA-I alleles - has not been fully characterized in cancer.

Pan-cancer analysis identifies mutations in that recapitulate mutant SF3B1 splicing dysregulation.

The gene encoding the core spliceosomal protein SF3B1 is the most frequently mutated gene encoding a splicing factor in a variety of hematologic malignancies and solid tumors. mutations induce use of cryptic 3' splice sites (3'ss), and these splicing errors contribute to tumorigenesis. However, it is unclear how widespread this type of cryptic 3'ss usage is in cancers and what is the full spectrum of genetic mutations that cause such missplicing.