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Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

Oncogene volume 25, pages 5837–5845 (2006)Cite this article

Abstract

Tumors arising in BRCA1 and BRCA2 mutation carriers appear to have specific pathological and gene expression profiles, which show a high level of concordance. BRCA1 tumors are high-grade, negative for hormone receptors, have a high proliferation rate, and are positive for some cell cycle promoter genes. BRCA2 tumors present a phenotype opposite to BRCA1 tumors but very similar to sporadic tumors, except that BRCA2 overexpress some DNA repair markers such as CHEK2, show high cytoplasmic expression of RAD51, and are negative for HER-2 amplification and expression. Some of these characteristics have also been found in cDNA expression studies, although more analysis are necessary in order to obtain new markers that can be associated with a germ line mutation in BRCA1 or BRCA2. In this way, some studies in normal tissues of BRCA1/2 carriers suggest that differences exist in the level of expression of some genes when compared with noncarriers. Finally, IHC studies in tumors carrying a mutation in CHEK2 are rare and show contradictory results, probably due to the low number of these cases. However, they represent an example showing how different mutations of the same gene may be associated with specific histological subtypes of cancer.

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Acknowledgements

This work was partially financed by grants from the Health and Science Ministries, FIS04-2240 and SAF03-02497 respectively. EH is financed by the Spanish Association Against Cancer (AECC).

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  1. Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain

    E Honrado, A Osorio & J Benitez

  2. Breast and Gynecological Cancer Group, Spanish National Cancer Centre (CNIO), Madrid, Spain

    J Palacios

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Honrado, E., Osorio, A., Palacios, J. et al. Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations. Oncogene 25, 5837–5845 (2006). https://doi.org/10.1038/sj.onc.1209875

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