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Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes

Oncogene volume 27, pages 3165–3175 (2008)Cite this article

Abstract

Five breast cancer subtypes have been described in sporadic breast cancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different genomic aberration patterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16 BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1-related tumors are preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.

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Abbreviations

aCGH:

array-based comparative genomic hybridization

CNA:

copy number of genomic aberrations

ER:

estrogen receptor

FBC:

familial breast cancer

GAP:

genomic aberration pattern

IHC:

immunohistochemical

SBC:

sporadic breast cancer

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Acknowledgements

We thank the Spanish National Tumor Bank Network, and Luz Álvarez and Miguel Urioste from the Familial Cancer Unit for the collection of the samples. For their technical assistance, we thank the Immunohistological Unit, and Carmen Martin and Juan C Cigudosa from the Molecular Cytogenetics Group, at the Spanish National Cancer Center and C Angelica Medina from Medical Genetics Division of the University of Pennsylvania. We also thank Susanna Leskelä for English assistance. LM Grant sponsor: Spanish Ministry of Education and Science FPU AP-2004-0448. Short stays sponsorships: ICRETT/05/063 and EMBO Short-Term Fellowship ASTF 162-05. MJG was supported by the Fundación Científica de la Asociación Española contra el Cáncer. This study has been partially funded by projects SAF03-02497 and SAF 06-06149 from the Spanish Ministry of Education and Science; and by a grant from Breast Cancer Research Foundation (BCRF) to KLN.

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Authors and Affiliations

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

    L Melchor, E Honrado, M J García, A Osorio & J Benítez

  2. Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain

    S Álvarez

  3. Breast and Gynecological Group, Molecular Pathology Program, Spanish National Cancer Center (CNIO), Madrid, Spain

    J Palacios

  4. Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA, USA

    K L Nathanson

  5. Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

    J Benítez

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  1. L Melchor
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Correspondence to J Benítez.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Melchor, L., Honrado, E., García, M. et al. Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene 27, 3165–3175 (2008). https://doi.org/10.1038/sj.onc.1210975

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