Intracystic Papillary Carcinoma of Breast Harbors Significant Genomic Alteration Compared with Intracystic Papilloma: Genome-wide Copy Number and LOH Analysis Using High-Density Single-Nucleotide Polymorphism Microarrays.
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Purpose: Intracystic papillary breast tumors consist of benign papilloma, carcinoma in situ and carcinoma with invasion. Using high-density single-nucleotide polymorphism arrays, this study aimed to determine the profile of genomic alterations in these lesions and to identify novel diagnostic criteria. Methods: Ten samples of intracystic papillary tumor, which included five papillomas (Pap), three papillary carcinomas in situ (PurePC) and two papillary carcinomas with invasion (PCinv), were studied. DNA was extracted from tumor and normal tissues that were microdissected from the same formalin-fixed paraffin embedded blocks. Using probe intensity and genotype data from high-density oligonucleotide SNP microarrays (AffymetrixR GeneChip Genome-wide Human 5.0), paired copy number and LOH analysis was performed using Partek Genomic Suite Software. Results: Quality control (QC) call rate, which is an index measuring the quality of a SNP microarray experiment, ranged from 70.75% to 91.93%, mean 80.72%. The mean total genomic alteration rate (sum of amplifications, deletions and copy-neutral loss of heterogeneity) with respect to the whole genome was 2.87%, 15.4% and 35.3% in Pap, PC and IDC, respectively, and was significantly different between samples (Kruskal-Wallis chi-squared test, p = 0.043). The most commonly altered regions (. 4/5) in papillary carcinoma were copy-neutral loss of heterogeneity at 3p21.31 and 3p14.2 and amplification at 20q13.13. Genes altered only in invasive carcinoma included genes concerned with transcription. Conclusions: Among intracystic papillary breast tumors, malignant tumors, including non-invasive tumors, which are difficult to diagnose histopathologically, harbor significant genomic alteration. Our findings may aid clinical management of these tumors and may provide insight into their carcinogenesis.
- 2011-06-09
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