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Estrogen Receptor Status Could Modulate the Genomic Pattern in Familial and Sporadic Breast Cancer

Authors' Affiliations: ¹ Human Genetics Group and ² Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO); ³ Center for Biomedical Research on Rare Diseases, Madrid, Spain; ⁴ Division of Medical Genetics, Department of Medicine, and Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; and ⁵ Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom

Requests for reprints: Javier Benítez, Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center, 28029 Madrid, Spain. Phone: 34-91-224-69-55; Fax: 34-91-224-69-23; E-mail: jbenitez{at}cnio.es.

Purpose: Familial breast cancer represents 5% to 10% of all breast tumors. Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases.

Experimental Design: To better characterize and define the genomic differences between the three classes of familial tumors and sporadic malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from familial breast cancer patients and 19 sporadic breast tumors using a 1-Mb resolution bacterial artificial chromosome array-based comparative genomic hybridization.

Results: We found that BRCA1/2 tumors showed a higher genomic instability than BRCAX and sporadic cancers. There were common genomic alterations present in all breast cancer groups, such as gains of 1q and 16p or losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen receptor (ER) may play a crucial role in driving tumor development through distinct genomic pathways independently of the tumor type (sporadic or familial) and mutation status (BRCA1 or BRCA2). ER^– tumors presented higher genomic instability and different altered regions than ER⁺ ones.

Conclusions: According to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to the genomic profile of abnormalities by increasing or modulating the genome instability.