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

Publication ,  Journal Article
Desouki, MM; Liao, S; Huang, H; Conroy, J; Nowak, NJ; Shepherd, L; Gaile, DP; Geradts, J
Published in: J Cancer Res Clin Oncol
May 2011

PURPOSE: 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. METHODS: 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. RESULTS: 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 localized to chromosomes 7p, 16q and 18q. In the MP-ML comparison, 131 BACs showed differential CNAs. Most of them were localized to chromosomes 1q and 20. By Q-PCR, seven candidate genes could be confirmed to show differential distributions of CNAs. TSPAN1 was amplified in UP and deleted in MP tumors. The gene was markedly downregulated in ER-negative and high-grade breast cancers. CONCLUSIONS: Metastasizing tumors had a higher rate of deletions, suggesting possible inactivation of metastasis suppressor genes. We provide preliminary evidence that TSPAN1 may be another important breast cancer suppressor gene belonging to the tetraspanin superfamily.

Duke Scholars

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Published In

J Cancer Res Clin Oncol

DOI

EISSN

1432-1335

Publication Date

May 2011

Volume

137

Issue

5

Start / End Page

795 / 809

Location

Germany

Related Subject Headings

  • Tetraspanins
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Membrane Proteins
  • Lymphatic Metastasis
  • Humans
  • Genes, Tumor Suppressor
  • Gene Dosage
  • Female
 

Citation

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Desouki, M. M., Liao, S., Huang, H., Conroy, J., Nowak, N. J., Shepherd, L., … Geradts, J. (2011). Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach. J Cancer Res Clin Oncol, 137(5), 795–809. https://doi.org/10.1007/s00432-010-0937-1
Desouki, Mohamed M., Shaoxi Liao, Huayi Huang, Jeffrey Conroy, Norma J. Nowak, Lori Shepherd, Daniel P. Gaile, and Joseph Geradts. “Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach.J Cancer Res Clin Oncol 137, no. 5 (May 2011): 795–809. https://doi.org/10.1007/s00432-010-0937-1.
Desouki MM, Liao S, Huang H, Conroy J, Nowak NJ, Shepherd L, et al. Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach. J Cancer Res Clin Oncol. 2011 May;137(5):795–809.
Desouki, Mohamed M., et al. “Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach.J Cancer Res Clin Oncol, vol. 137, no. 5, May 2011, pp. 795–809. Pubmed, doi:10.1007/s00432-010-0937-1.
Desouki MM, Liao S, Huang H, Conroy J, Nowak NJ, Shepherd L, Gaile DP, Geradts J. Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach. J Cancer Res Clin Oncol. 2011 May;137(5):795–809.
Journal cover image

Published In

J Cancer Res Clin Oncol

DOI

EISSN

1432-1335

Publication Date

May 2011

Volume

137

Issue

5

Start / End Page

795 / 809

Location

Germany

Related Subject Headings

  • Tetraspanins
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Membrane Proteins
  • Lymphatic Metastasis
  • Humans
  • Genes, Tumor Suppressor
  • Gene Dosage
  • Female