DF/HCC Program Affiliation

Member, Breast Cancer Program

Research Abstract

Dr. Wang’s major research interest is the genomics of breast cancers. The goals of his research are to subclassify invasive breast cancers at genetic levels in combination with gene expression profiling, characterize the disease-associated genetic aberrations, and discover genes critical for the pathogenesis of breast cancers. The major strategy of his research integrates microgenomic/ human single nucleotide polymorphism (SNP) array and gene expression array analysis in human breast tumors, clinical outcome of the patients and functional characterization of the candidate genes in vitro and in vivo. Using microgenomic approach with Human SNP array, he and his colleagues discovered genetic instability and signature chromosomal alterations in a basal-like subset of sporadic breast cancers, similar to BRCA1 germline mutation-associated cancers. The observation provides the rationale for development of a new neo-adjuvant therapy targeting genetic instability for basal-like breast cancers. With high density SNP array analysis for both uniparental chromosomal loss and DNA copy number, he and his colleagues discovered frequent X chromosome isodisomy in sporadic basal-like and BRCA1-associated breast cancers, which indicating the potential role of duplication of active X chromosome in pathogenesis of breast cancers. He and his colleagues are searching for critical genes on signature LOH regions 5q and 14q in basal-like breast tumors. Recently, he and his colleagues, using integrated genomic approach, discovered that the 8q22 amplification is associated with early distant recurrence of breast cancers, and currently investigate the functional relevance of the candidate genes on 8q22 in vitro using siRNA and gene transfection. They further demonstrated that Cyclin E2 overexpression induced tetraploidy-mediated colony formation of human mammary epithelial cells, and lysosomal associated protein tansmembrane 4B (LAPTM4B) induced lysosomal distribution of anthracyclines and resistance to these drugs in breast cancer cells. He proposed the involvement of multiple genes in the 8q22 amplicon in progression of breast cancers. He closely collaborates with Dr. Andrea Richardson in Pathology in their research and also with other investigators in two projects of DF/Harvard SPORE in Breast Caner. His major focus in these projects is using Affymetrix high density SNP array and molecular inversion probes (MIP) technologies to identify the patterns of chromosomal alterations and genetic instability associated with biology and treatment of BRCA1-associated and sporadic basal-like breast cancers, and metastasis in breast cancer patients.

Publications

• Wang ZC, Buraimoh A, Iglehart JD, Richardson AL. Genome-Wide Analysis for Loss of Heterozygosity in Primary and Recurrent Phyllodes Tumor and Fibroadenoma of Breast using Single Nucleotide Polymorphism Arrays. Breast Cancer Res Treat 2006 Jun; 97(3):301-9
  PMID: 16791486
• Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 2006 Feb; 9(2):121-32
  PMID: 16473279
• Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N, Harris LN, Richardson A, Neel BG, Gu H. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med 2006 Jan; 12(1):114-21
  PMID: 16369543
• Wang ZC, Lin M, Wei LJ, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, Iglehart JD, Richardson A. Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers. Cancer Res 2004 Jan 1; 64(1):64-71
  PMID: 14729609