Division of Medical Genetics

RESEARCH INTERESTS

Katherine L. Nathanson, M.D.

Dr. Nathanson's research focuses on understanding inherited genetic susceptibility to cancer. She focuses on three major primary cancer types and has several projects investigating susceptibility in other areas.

In collaboration with Dr. Barbara Weber, she has explored genetic susceptibility to breast cancer. She investigated the contribution of two known high penetrance genes, BRCA1 and BRCA2, to breast and ovarian cancer susceptibility. In addition, she has been interested in modifiers of penetrance in BRCA1 mutation carriers and completed a novel pilot project using methods of non-parametric linkage to identify regions that may contain modifying genes in BRCA1 mutation carriers. She also has used markers to define areas of loss of heterozygosity on chromosomes 4 and 5q in BRCA1 associated breast cancer. Finally, they are looking at single nucleotide polymorphisms in proteins within the BASC (BRCA1 associated genome surveillance) complex as modifiers of breast cancer penetrance in BRCA1 mutation carriers.

In prostate cancer, she has been collecting high-risk families as part of a collaboration within the Cancer Genetics Network. They are interested in characterizing the prostate tumors from high risk families using CGH (comparative genomic hybridization) microarray and understanding if there are differences in tumor profile based on known low to moderate risk variants. In testis cancer, she is setting up an association study in collaboration with Dvaid Vaughn and Peter Kanetsky to look at variants in candidate genes in testis cancer cases and controls as predisposition factors for testis cancer.

She has an interest in families with pancreatic cancer, and intends to screen family members at increased risk of pancreatic cancer, in collaboration with Anil Rustigi and Michael Kockman.

Finally, patients with pheochromocytoma can participate in a research protocol with Catherine Stolle, looking at mutations in all the known genes that predispose to that cancer.

Recent Publications

• Shih HA, Couch FJ, Nathanson KL, Rebbeck TR, Blackwood MA, Calzone K, Stopfer J, Seal S, Stratton MR, and Weber BL. BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic. J Clin Oncol, 20:994-9 Feb 2002.
• Thompson D, Szabo CI, Mangion J, Oldenburg RA, Odefrey F, Seal S, Barfoot R, Kroeze-Jansema K, Teare D, Rahman N, (14 additional authors), Nathanson KL, (22 additional authors), Easton DF, Goldgar DE, and Stratton MR. Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium. PNAS, 99:827-831 Jan 2002
• Nathanson KL, Shugart YY, Szabo C, Omaruddin R, Goldgar D, Rebbeck TR, Weber BL. CGH targeted linkage analysis reveals a possible BRCA1 modifier locus on chromosome 5q. Hum Molec Genet, 11:1327-32 May 2002.
• Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, (27 additional authors), Futreal PA, Nathanson KL, Weber BL, Rahman N, Stratton MR. CHK2 1100delC is a low penetrance familial breast cancer susceptibility allele except in BRCA1 and BRCA2 mutation carriers. Nat Genet, 31:55-59 May 2002.
• Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL , Weber BL. Penetrance estimates for BRCA1 mutation carriers identified in a cancer risk evaluation program. JNCI, 94: 1365-1372 September 2002.
• Letrero R, Weber BL, Nathanson KL . Resolving ATM haplotypes in Caucasians. Am J Hum Genetics, in press.