U2AF1

Overview

U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) is a splicing factor required for pre-mRNA splicing. The p.S34F hotspot mutation was identified in 3% of lung adenocarcinoma cases, representing the first report of U2AF1 mutations in an epithelial tumor. This mutation is associated with significantly reduced progression-free survival, making it a potential prognostic biomarker.

Alterations observed in the corpus

  • p.S34F hotspot mutation in 3% of LUAD cases (P = 2.0 x 10^-6); first report in an epithelial tumor; associated with reduced progression-free survival (P = 0.00011, log-rank) PMID:22980975
  • Co-occurred with NF1 mutations (P = 0.0011) in the Broad LUAD cohort PMID:22980975
  • Identified as a spliceosome-complex gene recurrently mutated in AML (200 cases; TCGA); spliceosome category had 14% overall prevalence PMID:23634996.
  • U2AF1 somatic splicing-factor mutations in 4 MPN patients; co-mutated with ASXL1 in myeloproliferative neoplasms alongside CALR discovery PMID:24325359
  • S34F mutations in 3% (8/230) of LUAD (TCGA); associated with 129 alternative splicing events including cassette exons and alternative 3’ splice sites; drives alternative splicing of CTNNB1. PMID:25079552
  • Identified as a significantly mutated spliceosome gene in the TCGA Pan-Lung comprehensive genomic characterization of 1,144 NSCLC cases (lung ADC and SqCC combined) PMID:27158780.
  • Splicing factor mutation in AML chromatin-spliceosome subgroup; clusters with SF3B1, SRSF2, ZRSR2 and chromatin regulators as an adverse-risk entity; 84% of chromatin-spliceosome patients were ELN intermediate-risk but experienced adverse outcomes PMID:27276561
  • Included in the 8-gene AmpliSeq amplicon panel (TP53, DNMT3A, IDH1, IDH2, ASXL1, SRSF2, U2AF1, SF3B1) and observed in AML/MDS patients on the 10-day decitabine trial; not reported as independently predictive of decitabine response. PMID:27959731
  • U2AF1 mutated in 0.5% of a 1,013-sample prostate cancer cohort; first significant nomination of splicing-factor mutations as a recurrent prostate-cancer alteration alongside SF3B1 PMID:29610475

Cancer types (linked)

  • LUAD: p.S34F in 3% of cases (Broad WES cohort, 183 tumors); independently associated with poor prognosis PMID:22980975

Co-occurrence and mutual exclusivity

Therapeutic relevance

Open questions

  • Functional significance of U2AF1 p.S34F in LUAD beyond prognostic impact has not been experimentally validated in this study PMID:22980975

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:23634996

This page was processed by entity-page-writer on 2026-05-15. - PMID:24325359

This page was processed by entity-page-writer on 2026-05-15. - PMID:25079552

This page was processed by entity-page-writer on 2026-05-15. - PMID:27276561

This page was processed by entity-page-writer on 2026-05-15. - PMID:27959731

This page was processed by entity-page-writer on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.