{"entity":{"id":"paper-herschkowitz-rb1-loss-basal-like-bcr-2008","kind":"paper","name":"The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas","aka":[],"tldr":"Loss of one copy of the RB1 gene was found in 72% of basal-like breast cancers, with low RB1 messenger RNA and high p16, and an RB1-loss expression signature predicted outcome and possibly chemotherapy response.","summary":"88 primary breast carcinomas and matched normal DNA were subtyped by expression and assessed for RB1 loss of heterozygosity with polymorphic markers. LOH was seen in 39% overall, 72% of basal-like and 62% of luminal B tumours, which also showed low RB1 mRNA; p16INK4a was highly expressed in basal-like tumours consistent with RB1 loss. An RB1-LOH signature was highly prognostic and a potential predictor of neoadjuvant chemotherapy response.","asOf":"2026-09-24","links":[{"label":"Herschkowitz et al., Breast Cancer Res 2008: RB1 loss in basal-like and luminal B carcinomas","url":"https://doi.org/10.1186/bcr2142"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18782450/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":["rb1","cdk4-6"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle"],"terms":[],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research","year":2008,"doi":"10.1186/bcr2142","pmid":"18782450","authors":"Herschkowitz JI, He X, Fan C, Perou CM.","paperType":"translational","findings":["RB1 loss of heterozygosity in 72% of basal-like and 62% of luminal B tumours (39% overall).","Low RB1 mRNA and high p16 in basal-like tumours; RB1-loss signature prognostic."],"whatItMeans":"Functional RB1 loss is part of basal-like biology, which explains why CDK4/6 inhibitors have not worked in TNBC and why the cell-cycle vulnerability there lies downstream of RB.","caveats":["88 tumours; loss of heterozygosity rather than biallelic inactivation.","Later sequencing puts RB1 mutation or deep deletion nearer 15 to 20%."],"changedPractice":false,"participants":88},"route":"/key-papers/paper-herschkowitz-rb1-loss-basal-like-bcr-2008/","neighbours":{"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"rb1","kind":"target","name":"RB1","route":"/targets/rb1/"}],"pathway":[{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"}],"person":[{"id":"charles-perou","kind":"person","name":"Charles M. Perou","route":"/people/charles-perou/"}],"journal":[{"id":"breast-cancer-research","kind":"journal","name":"Breast cancer research","route":"/journals/breast-cancer-research/"}]}}