Gene Copy Number Variation in Male Breast Cancer by aCGH

Stefania Tommasi,Orsetta Zuffardi,Giuseppina Iannelli,Wainer Zoli,Elena Rossi,Angelo Paradiso,Anita Mangia,Marcella Mottolese,Laura Ottini,Patrizia Chiarappa

doi:10.1155/2010/468280

Abstract

Background: Male breast cancer (MBC) is a rare disease and little is known about its etiopathogenesis. Array comparative genomic hybridization (aCGH) provides a method to quantitatively measure the changes of DNA copy number and to map them directly onto the complete linear genome sequences. The aim of this study was to investigate DNA imbalances by aCGH and compare them with a female breast cancer dataset.Methods: We used Agilent Human Genome CGH Microarray Kit 44B and 44K to compare genomic alterations in 25 male breast cancer tissues studied at NCC of Bari and 16 female breast cancer deposited with the Gene Expression Omnibus (GSE12659). Data analysis was performed with Nexus Copy Number 5.0 software.Results: All the 25 male and 16 female breast cancer samples displayed some chromosomal instability (110.93 alterations per patient in female, 69 in male). However, male samples presented a lower frequency of genetic alterations both in terms of loss and gains.Conclusion: aCGH is an effective tool for analysis of cytogenetic aberrations in MBC, which involves different biological processes than female. Male most significant altered regions contained genes involved in cell communication, cell division and immunological response, while female cell–cell junction maintenance, regulation of transcription and neuron development.

Highlights

Male breast cancer (MBC) is a rare pathology representing about 1% of breast cancers (BC) [9]
The prevalence of MBC increases with age and its susceptibility may result from rare mutations in high penetrance genes such as BRCA1 and BRCA2, in particular BRCA2 (4–40%) more than BRCA1 (4%) mutations [8]
Other genes seem to be involved in MBC such as PTEN which results mutated in 22% [31], and other low penetrance genes such as CHEK2, mutated in 9% of MBC cases [8]

Summary

Introduction

Male breast cancer (MBC) is a rare pathology representing about 1% of breast cancers (BC) [9]. The reports documenting genome-wide copy number changes by CGH on metaphase in MBC have shown similarity in the pattern of imbalances with respect to the chromosomal alterations described in female breast cancers (FBC) [1,17,25] suggesting a common etiology for the disease process in both sexes. Many of the genetic aberrations shared by MBC and FBC are common to other epithelial cancer types [10]. This is surprising, considering the different hormonal milieu in which the tumor develops and the established role of estrogens in promoting BC development and progression [5]. The aim of this study was to investigate DNA imbalances by aCGH and compare them with a female breast cancer dataset

Objectives

Methods

Results

Conclusion