Aug 4, 2010

Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach

Journal of Cancer Research and Clinical Oncology
Mohamed M DesoukiJoseph Geradts

Abstract

We employed a whole genome tumor profiling approach in an attempt to identify DNA copy number alterations (CNAs) and new candidate genes that are correlated with the metastatic potential of a primary breast carcinoma and with progression at the metastatic site. Fifty-four small (≤ 2 cm), high grade, ER-positive, formalin-fixed invasive ductal carcinomas were suitable for whole genome profiling analysis. Twenty-four of them did not form metastases within 5-10 years (unmatched primaries, UP). Thirty tumors had at least one synchronous axillary lymph node metastasis (matched primaries, MP; matched lymph node metastases, ML). Genomic DNA was hybridized to high density (19k) BAC arrays. Statistical analysis revealed differential distributions of CNAs between UP and MP and between MP and ML, respectively. We selected 27 candidate genes for validation experiments using quantitative (Q-)PCR of genomic DNA. For tetraspanin TSPAN1, we studied mRNA expression levels in a separate cohort of primary breast carcinomas and in breast cell lines. Matched primary (MP) tumors had a threefold higher rate of DNA copy number losses compared to UP tumors. In the UP-MP comparison, 186 BACs were differentially amplified or deleted. Most of them were lo...Continue Reading

Mentioned in this Paper

Ductal Carcinoma
Gene Dosage
Formalin
Metastasis Suppressor Genes
Candidate Disease Gene
Array-Based Comparative Genomic Hybridization
Neoplasms
Secondary Malignant Neoplasm of Lymph Node
Bacterial Artificial Chromosomes
TSPAN1

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