Genetic heterogeneity by comparative genomic hybridization in BRCAx breast cancers

The chromosomal changes in eight familial BRCAx breast cancers (i.e., negative for BRCA1 or BRCA2) were analyzed by comparative genomic hybridization (CGH) to investigate intratumor heterogeneity. This was the first step in a study of most frequent chromosomal aberrations in BRCAx familial breast ca...

Full description

Saved in:
Bibliographic Details
Published in:Cancer genetics and cytogenetics 2008-04, Vol.182 (2), p.75-83
Main Authors: Mangia, Anita, Chiarappa, Patrizia, Tommasi, Stefania, Chiriatti, Annalisa, Petroni, Stella, Schittulli, Francesco, Paradiso, Angelo
Format: Article
Language:English
Subjects:
Adult
Aged
Apoptosis Regulatory Proteins
BRCA1 Protein - genetics
BRCA2 Protein - genetics
Breast Neoplasms - genetics
Chromosome Aberrations
Chromosomes, Human - genetics
DNA, Neoplasm - genetics
Female
Genetic Heterogeneity
Genome, Human
Humans
In Situ Hybridization, Fluorescence
Male
Middle Aged
Mutation - genetics
Nucleic Acid Hybridization
Polymerase Chain Reaction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The chromosomal changes in eight familial BRCAx breast cancers (i.e., negative for BRCA1 or BRCA2) were analyzed by comparative genomic hybridization (CGH) to investigate intratumor heterogeneity. This was the first step in a study of most frequent chromosomal aberrations in BRCAx familial breast cancers. Laser microdissection analysis of paraffin tissue samples was followed by whole-genome amplification. CGH was performed on DNA isolated from two to three different cell groups per case to detect any cytogenetic aberrations in important clones that might have been missed when analyzing DNA extracted from large numbers of cells. The results were compared, to evaluate the influence of tumor heterogeneity on CGH, and the heterogeneity was confirmed comparing CGH with fluorescence in situ hybridization results. Different chromosomal aberrations were detected between adjacent clones within the same section, which highlights the utility of microdissection in addressing the problem of heterogeneity in whole-genome studies. Some chromosomal regions were more frequently altered in the eight BRCAx tumors; loss of 2q, 3p, 3q, 8p, 9p, and 15q and gains of 1p, 4p, 4q, 5p, 6q, 12q, and 19p were the most common. Further studies focusing on specific genes and sequences with more sensitive approaches, such as array-CGH, are warranted to confirm these findings.
ISSN:0165-4608
1873-4456
DOI:10.1016/j.cancergencyto.2008.01.002