Kristen K. White B.S., Clinical Laboratory Science University of North Carolina Chapel Hill, NC

I grew up in the North Carolina coastal city, Jacksonville, and first came to UNC Chapel Hill in the Fall of 1991 as an undergraduate.  I completed my BS degree in Clinical Laboratory Science in May 1995.  After graduation, I moved to Burlington, NC, to work in the Special Microbiology Laboratory for Laboratory Corporation of America.  I processed, isolated and identified Mycobacterium sp. from clinical specimens and performed drug resistance testing.  I also spent limited time in the Mycology lab.  I left LabCorp to work for Dr. William B. Coleman in January 2002.  My husband and I live in Burlington and have completed building our first home.  We have one son, Matthew, born in January 2005 and our first four legged family member, Buckeye. We enjoy visiting family and friends at the beach and taking our son to Emerald Pointe waterpark.

Investigation of a Novel +ACA BRCA1 Promoter Polymorphism and Its Impact  on the Breast Cancer Susceptibility Phenotype  The BRCA1 breast cancer susceptibility gene is mutated in many hereditary breast cancers, and may be involved in sporadic breast cancer through non-mutational mechanisms. We have discovered a novel +ACA polymorphism at -600bp from the start of exon 1a in the BRCA1 minimal promoter region, resulting in ACATAACAC to ACATAACAACAC.  Among hereditary breast cancer patients the +ACA allele was detected in 13/24 (54%) BRCAx patients and in 8/17 (47%) mutant BRCA1 patients.  17/39 (44%) unaffected individuals carry the +ACA allele. The +ACA allele creates a core binding site for FAC1 transcriptional repressor protein (ACAACA). Electrophoretic mobility shift analyses demonstrate that FAC1 preferentially binds the +ACA BRCA1  promoter in comparison with the wild-type BRCA1 promoter. While the expression of FAC1 in normal breast epithelium or breast tumors has not yet been established by our laboratory, we have observed that breast tumors homozygous for the +ACA allele express lower levels of BRCA1 protein than tumors that are homozygous wild-type. Additionally, Van de Vijver et al. reported FAC1 upregulation in 77% of the breast carcinomas in their microarray studied. It is intriguing to speculate that the presence of this polymorphism in conjunction with aberrant FAC1 expression may negatively affect the normal activity of the BRCA1 promoter resulting in reduced expression of BRCA1 and increased susceptibility to breast carcinogenesis.   Current studies in our laboratory are aimed at (i) determining the frequency of this +ACA polymorphism in the general population, (ii) determining the frequency of this +ACA polymorphism in patients with hereditary and sporadic breast cancer, (iii) investigate the expression of the FAC1 in breast cancer and determine if FAC1 represses the expression of the BRCA1 in breast cancer, and (iv) directly examine the effect of the +ACA polymorphism on BRCA1 promoter function.

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