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Abstract

Breast cancer is a lethal cancer in women. It is urgent to identify new therapeutic biomarkers to facilitate the treatment. Therapeutic drug Herceptin (trastuzumab) is effective in Her2-positive breast cancer treatment, however, there is inconsistency to distinguish responders versus non-responders using Her2 as a sole biomarker. The human GT198 gene is a breast and ovarian cancer gene at chromosome 17q12, 2.9 Mb proximal from the ERBB2 gene encoding Her2. Both germline mutations and high frequency somatic mutations in GT198 are present in breast and ovarian cancer. In breast and ovarian tumors, somatic mutations are present in tumor stromal stem cells. Gene copy number increase of GT198 has also been found in breast cancer. Here we find that Her2 and GT198 proteins are co-expressed in breast tumor stromal cells carrying GT198 mutations, suggesting that Herceptin may in fact also target GT198-positive tumor stromal cells. Her2 gene amplicons generally encompass large genomic regions, thus the two adjacent genes may co-amplify and result in coexpression. Our finding suggests that GT198/Her2 double positivity is potentially a more specific therapeutic marker for Herceptin. In particular, positive tumor stroma, in addition to tumor, deserves more attention in clinical decisions. Since herceptin is extensively used in the treatment of breast cancer and GT198 is a causative breast cancer gene, this study provides insights into novel mechanisms associated with herceptin efficacy and reveals new biomarker using GT198 for improved targeted therapy.

Biography

Email: LKO@augusta.edu