Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer

The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole‐genome study of 166 archival est...

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Published in:Genes chromosomes & cancer 2008-12, Vol.47 (12), p.1049-1066
Main Authors: Loo, L. W. M., Ton, C., Wang, Y.-W., Grove, D. I., Bouzek, H., Vartanian, N., Lin, M.-G., Yuan, X., Lawton, T. L., Daling, J. R., Malone, K. E., Li, C. I., Hsu, L., Porter, P. L.
Format: Article
Language:English
Subjects:
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinoma, Ductal, Breast - genetics
Carcinoma, Lobular - genetics
Carcinoma, Lobular - pathology
Case-Control Studies
DNA, Neoplasm - metabolism
Female
Gene Expression Profiling
Humans
Immunohistochemistry
Loss of Heterozygosity
Polymorphism, Single Nucleotide
Receptors, Estrogen - analysis
Receptors, Estrogen - genetics
Tissue Array Analysis
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Summary:The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole‐genome study of 166 archival estrogen receptor (ER)‐positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip® Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high‐frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low‐grade IDC grouped together by virtue of LOH in 16q. Published 2008 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.20610