Patterns of chromosomal imbalances in invasive breast cancer

Invasive breast carcinomas are characterized by a complex pattern of chromo somal alterations. We applied comparative genomic hybridization (CGH) to an alyze 105 primary breast carcinomas using histograms to indicate the incide nce of DNA imbalances of tumor subgroups and difference histograms to compa re invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive an d -negative tumors (ER+/ER-). Only single imbalances showed a higher incide nce in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, an d 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imba lances showing statistical significance were also observed in G3 and ER-tum ors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 1 0q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18 p11-q11, and 20q, suggesting that they contribute to a more aggressive tumo r phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER+ tumors. The ratio pro files of all cases as well as histograms are accessible at our CGH online t umor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imb alances may serve as markers for a genetic classification of invasive breas t cancer. (C) 2000 Wiley-Liss, Inc.