The functional loss of the retinoblastoma tumor suppressor is a common event in basal-like and Luminal B breast carcinomas
Public Deposited- Creator
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Herschkowitz, Jason I
- Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
- Other Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine
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He, Xiaping
- Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
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Fan, Cheng
- Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
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Perou, Charles
- Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
- 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.
- Date of publication
- September 9, 2008
- DOI
- Identifier
- 18782450
- https://doi.org/10.1186/bcr2142
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Jason I Herschkowitz et al.; licensee BioMed Central Ltd.
- License
- Journal title
- Breast Cancer Research
- Journal volume
- 10
- Journal issue
- 5
- Page start
- R75
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1465-5411
- Bibliographic citation
- Breast Cancer Research. 2008 Sep 09;10(5):R75
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- January 27, 2017
Relations
- Parents:
This work has no parents.
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