Carol L. Rosenberg, MD
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PI: Carol L. Rosenberg, MD Title: Associate Professor of Medicine and Pathology Research interests: Translational research in breast cancer Clinical interests: Breast and gynecological cancers |
Personnel:
Pamela Larson, PhD
Lyndsey Emery (pre-doc)
Kelly Graham (pre-doc)
Bethany Hannafon (pre-doc)
Kristina Perry (pre-doc)
Research Summary:
This lab investigates the molecular and genetic alterations that are important early in human breast carcinogenesis. Our overall goal is to identify the abnormalities characterizing early cancer development, even before the tissue is histologically fully malignant. We hypothesize that these genetic abnormalities are biologically meaningful and clinically relevant. In testing this hypothesis, we have shown that cancer-related DNA and RNA abnormalities can be present in hyperplastic lesions and even in histologically normal epithelium. We study primary human tissues, and we ask questions and employ techniques suitable to that material, including laser capture microdissection, loss of heterozygosity and copy number alteration, mRNA and miRNA expression measured by microarray and quantitative PCR, and immunohistochemistry. By definition, the work is multidisciplinary, and collaborations with clinical pathologists, geneticists, surgeons and bioinformaticians and biostatisticians are crucial. In addition, we have projects ongoing with organizations both inside and out side BUMC, including the Framingham Heart Study and the Nurses’ Health Study-Benign Breast Disease Substudy. Identifying and understanding the landscape of molecular and genetic abnormalities in premalignant and histologically normal tissue should generate novel markers of breast cancer risk, uncover mechanisms implicated early in tumorigenesis, and identify new targets for cancer prevention and treatment.
This work has been supported with funds from the NIH, the Department of Defense, the Susan G Komen, Mary Kay Ash and Avon Foundations and the LaPann Funds.
Selected Recent Publications
Schlechter BL, Yang Q, Larson PS, Golubeva A, Blanchard RA, de las Morenas A, Rosenberg CL. Quantitative DNA fingerprinting may distinguish new primary breast cancers from disease recurrence. J Clin Oncol 2004; 22:1830-1838.
King C, Guo N, Frampton GM, Gerry NP, Lenburg ME, Rosenberg CL. Reliability and reproducibility of high-density oligonucleotide arrays using independently isolated and amplified small-sample RNA from in vivo tissue. J Molec Diagnostics 2005; 7:57-64.
Larson PS, Schlechter BL, de las Morenas A, Cupples LA, Garber JE, Rosenberg CL. Allele imbalance, or loss of heterozygosity, in normal-appearing breast epithelium of sporadic cancer cases and BRCA1 gene mutation carriers is increased compared with reduction mammoplasty tissues. J Clin Oncol 2005; 23:8613-8619.
Larson PS, de las Morenas A, Cerda SR, Bennett SR, Cupples LA, Rosenberg CL. Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors. J Pathol 2006; 209:306-317. [Epub ahead of print 2006 Apr 7 DOI 10.1002/cncr.22223].
Larson PS, Ungarelli R, de las Morenas A, Cupples LA, Rowlings K, Palmer JR, Rosenberg CL. In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast tissue. Cancer 2006; 107:2122-6. [Epub ahead of print 2006 Sep 22 DOI 10.1002/cncr.22223].
Murabito JM, Rosenberg CL, Finger D, Kreger B, Larson MG, Splansky GL, Antman KH, Hwang S-J. A genome-wide association study of breast and prostate cancer in the NHLBI’s Framingham Heart Study. BMC Medical Genetics 2007; 8 (Suppl 1):S6. doi:10.1196/1471-2350-8-S1-S6
Tripathi A, King CL, de las Morenas A, Perry VK, Burke B, Antoine G, Hirsch E, Kavanah M, Mendez J, Stone MD, Gerry NP, Lenburg M, Rosenberg CL. Gene expression abnormalities in histologically normal epithelium of breast cancer patients. Int J Cancer 2008; 122:1557-1566. [Epub ahead of print 2007 Nov 30 DOI 10.1002/ijc.23267].
Larson PS, Schlechter BL, King CL, Glass CH, Yang Q, Mack C, Pistey R, de las Morenas A, Rosenberg CL. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer. BMC Cancer 2008, 8:68.
