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Breast Cancer Susceptibility and Heterogeneity in Premalignant Lesions

Ductal Carcinoma in Situ (DCIS) detection rates have dramatically increased because of the widespread use of screening mammography. However, understanding of the biology and clinical behavior of DCIS is still limited, and there is no accurate risk assessment currently available to determine which patients with DCIS are at the greatest risk of developing an invasive carcinoma in their lifetime. The focus of my laboratory is to apply genome-wide allele-specific expression (ASE) analysis to identify novel risk alleles for DCIS progression by studying intra-individual DCIS heterogeneity. Current research projects include: (1) Identification of novel breast cancer risk loci in a post-GWAS era by global differential allele-specific expression (DASE); (2) Role of long non-coding RNAs and other genetic factors in DCIS progression; (3) Evaluation of intra-individual heterogeneity in DCIS lesions; (4) Identification of novel serum biomarkers for breast cancer early detection. Our long-term research goal is to identify differences among normal, pre-malignant and cancerous breast tissue, determine their consequences, and use this information to improve patient care.

1. Gao C, Devarajan K, Zhou Y, Slater CM, Daly MB, Chen X. Identifying breast cancer risk loci by global differential allele-specific expression (DASE) analysis in mammary epithelial transcriptome. BMC genomics 2012; 13: 570. PubMed
2. Chen X, Weaver J, Bove BA, Vanderveer LA, Weil SC, Miron A, Daly MB, Godwin AK. Allelic Imbalance in BRCA1 and BRCA2 Gene Expression Is Associated with an Increased Breast Cancer Risk. Hum Mol Genet. 2008;17:1336-48. PubMed
3. Chen X, Truong TT, Weaver J, Bove BA, Cattie K, Armstrong BA, Daly MB, Godwin AK. Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression. Human Mutation. 2006;27:427-35. PubMed
4. Chen X, Arciero CA, Wang C, Broccoli D, Godwin AK. BRCC36 is essential for IR-induced BRCA1 phosphorylation and nuclear foci formation. Cancer Res. 2006;66:5039-46. PubMed
5. Schilder RJ, Sill M W, Chen X, Darcy KM, Decesare SL, Lewandowski G, Lee RB, Arciero CA, Wu H, Godwin AK. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res. 2005;11:5539-48. PubMed