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The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas.

Abstract：

INTRODUCTION:Breast cancers can be classified using whole genome expression into distinct subtypes that show differences in prognosis. One of these groups, the basal-like subtype, is poorly differentiated, highly metastatic, genomically unstable, and contains specific genetic alterations such as the loss of tumour protein 53 (TP53). The loss of the retinoblastoma tumour suppressor encoded by the RB1 locus is a well-characterised occurrence in many tumour types; however, its role in breast cancer is less clear with many reports demonstrating a loss of heterozygosity that does not correlate with a loss of RB1 protein expression. METHODS:We used gene expression analysis for tumour subtyping and polymorphic markers located at the RB1 locus to assess the frequency of loss of heterozygosity in 88 primary human breast carcinomas and their normal tissue genomic DNA samples. RESULTS:RB1 loss of heterozygosity was observed at an overall frequency of 39%, with a high frequency in basal-like (72%) and luminal B (62%) tumours. These tumours also concurrently showed low expression of RB1 mRNA. p16INK4a was highly expressed in basal-like tumours, presumably due to a previously reported feedback loop caused by RB1 loss. An RB1 loss of heterozygosity signature was developed and shown to be highly prognostic, and was potentially a predictive marker of response to neoadjuvant chemotherapy. CONCLUSIONS:These results suggest that the functional loss of RB1 is common in basal-like tumours, which may play a key role in dictating their aggressive biology and unique therapeutic responses.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Herschkowitz JI,He X,Fan C,Perou CM

doi

10.1186/bcr2142

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

R75

issue

5

eissn

1465-5411

issn

1465-542X

pii

bcr2142

journal_volume

10

pub_type

杂志文章

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