RB1

Overview

RB1 encodes the retinoblastoma tumor suppressor protein, a master regulator of the G1/S cell cycle checkpoint. Loss-of-function mutations and homozygous deletions in RB1 are recurrent in hepatocellular carcinoma (HCC) and provide rationale for CDK4/6 inhibitor trials.

Alterations observed in the corpus

  • Loss-of-function mutation in 4% of HCCs (WES, n=1,289 patients). PMID:24798001
  • Homozygous deletion in 5% of HCCs (SNP-array, n=704 patients). PMID:24798001
  • Focal copy number loss on 13q identified as a recurrently altered CNA in prostate cancer prostatectomy cohorts (prad_mskcc, prad_mskcc_2014). PMID:25024180
  • Mutated in 4% of LUAD (TCGA, n=230); frameshift indels enriched in transversion-low (TL) adenocarcinomas vs SCLC (P < 0.05). PMID:25079552
  • Significantly mutated across a 25-sample muscle-invasive urothelial carcinoma cohort (MutSigCV), consistent with a major tumor-suppressor role in bladder cancer PMID:25096233
  • p53-p21-RB1 pathway remains intact in EWS::FLI1-expressing human embryonic mesenchymal stem cells (heMSCs); RB1 induction limits long-term in vitro culture of transduced cells in the Ewing sarcoma cell-of-origin model PMID:25186949
  • Heterozygous loss with no detectable protein in 3/7 MSK prostate cancer cell lines; complete deletion in MSK-PCa5 detected only by RNA-seq; represents an RB-pathway tumor-suppressor hit in castration-resistant prostate cancer models PMID:25201530
  • RB1 tumor suppressor mutations identified in 15/402 (3.7%) PTCs alongside TP53, NF1, NF2, and MEN1; part of the tumor suppressor gene alteration cluster in PTC. PMID:25417114
  • Tumor suppressor with mutations in a metastatic cSCC cohort (n=29); component of cell-cycle regulatory defects in cSCC PMID:25589618
  • Mutated in 3% of HNSCC (n=279); structural alterations more often inactivating than coding fusions PMID:25631445
  • In HCC, RB1 is a component of the cell-cycle/RB axis altered in 49% of cases; CDKN2A loss is enriched in alcohol-related HCC. PMID:25822088
  • In PAAD, RB1 loss occurs in 3% of cases as part of the RB pathway (dominated by CDKN2A/B deletion, 36% each); co-occurs with CDK4 amplification (9%) and CCND1 amplification (6%). Also identified in KRAS-wildtype PDA cases. PMID:25855536
  • In mCRPC, RB1 loss occurs in 21% of cases; part of the cell-cycle pathway aberrations potentially actionable via CDK4 inhibition. PMID:26000489
  • In cutaneous melanoma (SKCM), RB1 is mutated in 12 cases, all in UV-signature samples, enriched in the NF1 subtype; part of the RB1/CDKN2A cell-cycle pathway altered in 69% of 318 cases. PMID:26091043
  • Bi-allelic loss in 93% of non-chromothriptic SCLC tumours; many alterations at exon–intron junctions cause protein-damaging splice events; frequent complex translocations; universal TP53/RB1 loss argued to be obligatory in SCLC pathogenesis. PMID:26168399
  • Absent (0/59) in high-grade upper tract urothelial carcinoma (UTUC) vs 18.6% in high-grade urothelial carcinoma of the bladder (UCB) (p<0.001); striking depletion relative to UCB. PMID:26278805
  • Loss-of-function mutations in desmoplastic melanoma; IHC-confirmed protein loss. PMID:26343386
  • Identified as a marker of the reactive-like ILC mRNA subtype in a TCGA/METABRIC integrated analysis of invasive lobular carcinoma PMID:26451490
  • Heterozygous loss often co-incident with BRCA2 loss at 13q in primary prostate cancer PMID:26544944
  • 13q14.2 deletion in 4/25 (16%) Sézary syndrome PMID:26551667
  • Deletion in 70% of CRPC-NE vs. 32% of CRPC-Adeno (P = 0.003); concurrent RB1+TP53 loss in 53.3% of CRPC-NE (P < 0.0004) PMID:26855148
  • RB1 infrequently truncated in a targeted-sequencing study of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC). PMID:26878173
  • RB1 frequently mutated in plasmacytoid-variant bladder cancer at frequencies similar to urothelial carcinoma NOS. PMID:26901067
  • RB1 loss in mCRPC associated with elevated CCP score, elevated E2F1 expression, and a 15-gene Fanconi anaemia signature; E2F1 high expression correlates with CCP (r=0.8, P<0.001) and FA pathway activity (r=0.78, P<0.001). PMID:26928463
  • Confirmed as a significantly mutated gene (pan-cancer tumor suppressor) in a 619-case colorectal carcinoma WES cohort (NHS/HPFS); newly statistically designated as a CRC driver gene due to cohort size. PMID:27149842
  • One of six genes significantly mutated in both lung ADC and lung SqCC histologies in the 1,144-tumor NSCLC landscape study (alongside TP53, ARID1A, CDKN2A, PIK3CA, NF1); sex-specific enrichment: RB1 mutations enriched in females in lung SqCC (FDR q < 0.1). PMID:27158780
  • Identified as a Mut-driver in the METABRIC 2,433-tumor breast cancer cohort (cell-cycle TSG); co-mutation of TP53+RB1 (OR=5.3) is characteristic of triple-negative breast cancers. PMID:27161491
  • RB1 alterations found in 3/20 (15%) recurrent/metastatic HPV-positive HNSCC; co-mutation with TP53 associated with elevated chromosomal instability PMID:27442865.
  • Combined ATM/RB1/FANCC alteration signature present in 73.3% of pre-chemotherapy urothelial carcinoma tumors but only 37.9% of post-chemotherapy tumors (p=0.05), suggesting selective elimination of RB1-altered clones by cisplatin-based chemotherapy PMID:27749842
  • Loss-of-function mutations in 5% of HR+/HER2− metastatic breast cancer (vs <1% in early breast cancer, p=0.008, FDR=0.09); mostly truncating; implies potential primary resistance to CDK4 inhibitors (palbociclib) since RB1 is required for palbociclib bioactivity PMID:28027327
  • Germline splice-site c.1216-3A>G in osteosarcoma (OS) — increased risk for second cancers; returned as clinically impactful germline finding in a pediatric precision-oncology cohort PMID:28007021
  • Recurrently deleted at 13q14.2 in esophageal squamous cell carcinoma (ESCC) in a multi-platform genomic study of gastroesophageal adenocarcinoma PMID:28052061
  • Recurrent baseline alteration in SCLC consistent with near-universal RB1 loss; preserved through acquired chemotherapy resistance in PDX models; no evidence of acquired driver mutations under chemotherapy selection PMID:28196596
  • Cell-cycle pathway gene with alterations more common at higher stage/grade in non-muscle-invasive bladder cancer (NMIBC; n=105) PMID:28583311
  • Altered in 68/500 (13.6%) in the MET500 pan-cancer metastatic cohort; also fusion-disrupted in 6 cases; germline PPGM enrichment noted PMID:28783718
  • Frequency rises sharply with castration resistance in prostate cancer (2% noncastrate → 18% mCRPC); locoregional-to-mCRPC progression is marked by convergent PTEN and RB1 co-loss PMID:28825054
  • RB1 has recurrent point mutations in addition to historically described copy-number losses in DLBCL PMID:28985567
  • RB1 mostly inactivating mutations (17%) in MIBC with associated reduced mRNA; hallmark co-event with TP53 loss in the neuronal subtype PMID:28988769
  • RB1 is a pan-sarcoma SMG with deep deletions in 14% LMS, 16% UPS, 24% MFS; enriched mutations in STLMS iCluster C1 (p=0.04) PMID:29100075
  • Confirmed established prostate-cancer driver with enrichment in metastatic vs. primary disease in a WES meta-analysis of 1,013 prostate tumors (prad_p1000); included in the metastasis-enrichment genomic signature proposed for prospective risk stratification PMID:29610475.

Cancer types (linked)

  • HCC — RB1 LOF in 4% and homozygous deletion in 5%; provides mechanistic rationale for CDK4/6 inhibitor trials (e.g., palbociclib in RB1-positive disease). PMID:24798001

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data with specific partner genes reported in the current corpus.

Therapeutic relevance

Open questions

  • No CDK4/6 inhibitor has been validated in a biomarker-selected RB1-deficient HCC phase III trial.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15. - PMID:29100075

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

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