SF3B1

Overview

SF3B1 is a core splicing factor recurrently mutated in hematologic malignancies. In the corpus it is the single most frequently mutated driver in CLL.

Alterations observed in the corpus

  • Mutated in 17.5% of patients in the 1,148-patient CLL map — the most frequent cardinal CLL driver, ahead of NOTCH1 (12.3%), ATM (11.2%), and TP53 (9.1%) PMID:35927489.
  • R625C hotspot mutation identified in 1 of 7 treatment-refractory lactotroph pituitary neuroendocrine tumors (PitNETs); previously reported in aggressive prolactinomas PMID:38758238.
  • SF3B1 splicing-factor mutations are recurrent in MDS and co-occur with STAG2 mutations in the Tokyo cohort PMID:21909114
  • WES of 103 breast cancers identified SF3B1 as a recurrently mutated splicing-factor gene, with mutations associated with altered RNA splicing patterns PMID:22158541
  • Identified as a significantly mutated gene in breast cancer WES of 100 tumors, with recurrent mutations in the RNA splicing factor SF3B1 PMID:22722201
  • Identified as a significantly mutated splicing factor gene in TCGA breast cancer cohort (510 tumors) PMID:23000897
  • Among significantly mutated genes in pancreatic cancer WES of 142 ICGC tumors PMID:23103869
  • Recurrently mutated in CLL WES of 160 tumors (Broad Institute cohort); SF3B1 mutations are a hallmark of CLL and associate with distinct clinical features PMID:23415222
  • SF3B1 is a recurrent spliceosome-complex gene mutated in AML (14% prevalence alongside U2AF1 and SRSF2) PMID:23634996
  • Truncating mutation identified in the discovery cohort of adenoid cystic carcinoma (24 cases); classified among known cancer/tumor-suppressor genes with loss-of-function mutations in ACC. PMID:23778141
  • SF3B1 somatic splicing-factor mutation identified in 3 MPN patients alongside other epigenetic/splicing co-mutations in a CALR-discovery exome-sequencing study PMID:24325359
  • R625H hot-spot mutation co-occurring with GNAQ/GNA11 in the Triple-WT cutaneous melanoma subtype. PMID:26091043
  • Non-passenger somatic mutation in breast AdCC (adenoid cystic carcinoma of the breast); shared with salivary gland AdCCs; one of several cancer genes mutated in WES of 12 breast AdCC tumours (0.27 non-silent mutations/Mb, no TP53 or PIK3CA mutations) PMID:26095796
  • Recurrent K700E hotspot (>50% of all SF3B1 mutations) in CLL; mutated in 184/1,009 (18.2%) CLLmap patients; 51% of SF3B1 mutations co-occur with del(13q); SF3B1-mut/del(13q) double-mutant subtype has shorter time to first therapy and inferior OS (P=0.0002); Sf3b1-K700E drives alternative splicing of NFATC1 and 375 other genes, activating mTORC1/MYC pathways PMID:26200345
  • Associated with shorter PFS in CLL patients on frontline fludarabine-based chemoimmunotherapy (CLL8 trial); CCF as likely to rise as fall on therapy; 9 instances of multiple distinct alleles per CLL indicating convergent evolution PMID:26466571
  • 3 mutations in uveal melanoma: p.R625C, p.R625H, p.K666T PMID:26683228
  • Low-frequency recurrent mutation in thyroid cancer (PDTC/ATC), detected alongside other low-frequency hits in a targeted sequencing study PMID:26878173
  • Co-listed with CMTR2/FTSJD1 and SNRPD3 as recurrently mutated splicing factors in lung ADC, in a 1,144-NSCLC exome-sequencing cohort PMID:27158780.
  • Recurrent K700E mutation in 3.5% of ER+ breast tumours (ONC=52%); linked to differential splicing; associated with older age at diagnosis (OR=4.5) and mutually exclusive with TP53 (OR=0.049) in the 2,433-tumour METABRIC cohort PMID:27161491.
  • Splicing factor mutation; part of the chromatin-spliceosome subgroup in AML (n=1,540); co-occurs with ASXL1, SRSF2, U2AF1, and ZRSR2 as an adverse-risk cluster PMID:27276561
  • Alongside TP53, the only gene whose mutations consistently declined to VAF <5% during 10-day decitabine therapy in AML/MDS patients (N=116 combined cohort); included in both the 264-gene enhanced exome and the 8-gene AmpliSeq panel used on this trial. PMID:27959731
  • Newly nominated CCA driver; mutated in 4.6% at hotspots codon 625 (23%) and codon 700 (14%), implicating splicing dysregulation paralleling uveal melanoma and breast cancer hotspots PMID:28667006
  • Top CRISPR-essential dependency in DLBCL; mutated in the corpus alongside MTOR PMID:28985567
  • SF3B1 K700E used as the empirical AC=16 cutoff for the ‘Common in ExAC’ filter in the TCGA MC3 mutation calling pipeline — highest ExAC count observed for a known clonal-hematopoiesis somatic event in the non-TCGA subset of ExAC v0.3.1 PMID:29596782
  • SF3B1 mutated in 1.1% of a 1,013-sample prostate cancer cohort; mutations cluster in C-terminal HEAT repeats. First significant nomination of splicing-factor mutations as a recurrent prostate-cancer alteration alongside U2AF1 PMID:29610475

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • Part of the cardinal SF3B1/NOTCH1/ATM/TP53 driver set PMID:35927489.

Therapeutic relevance

  • No direct therapeutic link reported in the corpus.

Open questions

  • Relationship between SF3B1 mutations and the 8 prognostic gene expression clusters identified in the CLL map PMID:35927489.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:21909114

This page was processed by entity-page-writer on 2026-05-15. - PMID:22158541

This page was processed by entity-page-writer on 2026-05-15. - PMID:22722201

This page was processed by entity-page-writer on 2026-05-15. - PMID:23000897

This page was processed by entity-page-writer on 2026-05-15. - PMID:23103869

This page was processed by entity-page-writer on 2026-05-15. - PMID:23415222

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:23778141

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:26091043

This page was processed by entity-page-writer on 2026-05-15. - PMID:26095796

This page was processed by entity-page-writer on 2026-05-15. - PMID:26200345

This page was processed by entity-page-writer on 2026-05-15. - PMID:26466571

This page was processed by entity-page-writer on 2026-05-15. - PMID:26683228

This page was processed by entity-page-writer on 2026-05-15. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27161491

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:28667006

This page was processed by wiki-cli on 2026-05-15. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

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