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Breast Cancer Research
Published in: Breast Cancer Research 5/2008

Open Access 01-10-2008 | Research article

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

Authors: Jason I Herschkowitz, Xiaping He, Cheng Fan, Charles M Perou

Published in: Breast Cancer Research | Issue 5/2008

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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.
Appendix
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Metadata
Title
The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas
Authors
Jason I Herschkowitz
Xiaping He
Cheng Fan
Charles M Perou
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2142

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