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

Loo, L W M and Ton, C and Wang, Y-W and Grove, D I and Bouzek, H and Vartanian, N and Lin, M-G and Yuan, X and Lawton, T L and Daling, J R and Malone, K E and Li, C I and Hsu, L and Porter, P L (2008) Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer. Genes, chromosomes & cancer, 47 (12). pp. 1049-1066. ISSN 1098-2264

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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(R) 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.

Item Type: Article or Abstract
Additional Information: This article is a U.S. Government work and is in the public domain. See the original article posting at:
DOI: 10.1002/gcc.20610
PubMed ID: 18720524
PMCID: PMC2871767
Grant Numbers: R01 CA095717-04, R01 CA085913-05
Keywords or MeSH Headings: 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
Subjects: Cellular and Organismal Processes > Genetic processes > Mutation
Diseases > Solid tumors > Breast cancer
Depositing User: Library Staff
Date Deposited: 23 Oct 2008 20:54
Last Modified: 14 Feb 2012 14:42

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