Poster abstracts

Poster number 74 submitted by Cindy Lee

MYCBP: a novel genetic explanation for the loss of DNA repair in breast cancer

Cindy Lee (Biomedical Informatics, The Ohio State University), Jeffrey Parvin (Biomedical Informatics, The Ohio State University)

Abstract:
Purpose: Deficient BRCA confers a 54-90% lifetime risk of breast cancer but only accounts for 20% of familial breast cancer. We identify other genetic factors in breast cancer by studying proteins that could perform similar functions to BRCA and might function in the same pathways as known breast cancer susceptibility genes.

Methods: We screened 70 breast cancer gene expression datasets for candidate genes that were coexpressed with genes in the BRCA DNA repair pathways. MYCBP, c-Myc Binding Protein, coexpressed with four DNA repair factors; differentially expressed in breast carcinomas versus normal tissue; and demonstrated an effect on 3 DNA repair pathways.
We hypothesize that MYCBP plays a role in DNA repair and propose testing function in DNA repair pathways, investigating MYCBP regulation of repair gene transcription, and evaluating the potential of MYCBP to be a biomarker in breast cancer.

Results & Implications:
DNA repair: Similar to known DNA repair genes, MYCBP depletion results in a 5-fold decrease in DNA repair.
Transcriptional regulation: MYCBP depletion results in a loss of DNA repair factors BRCA1, RAD51, and 53BP1 (protein, RNA). The decrease in repair factor expression shows the basis for MYCBP having such a profound effect on multiple DNA repair pathways. The loss of these genes essential to three different DNA repair pathways increases the likelihood of downstream carcinogenesis.
Tumor sample expression: We stained human breast tissue samples with MYCBP antibody found differential staining between normal and cancer tissue. Data on MYCBP expression patterns in tumor samples can provide insight in patient diagnosis.
Cancer therapy response: We have tested cisplatin on MYCBP-deficient cells, which show sensitivity to the drug. Cisplatin is a common cancer therapeutic; however, some patients have shown resistance to its application. Determining root cause and likely response through MYCBP will help personalize patient care.

Keywords: MYCBP, doublestrand break repair