Abstract A60: DOK1 gene may act as a tumor suppressor in breast cancer

Abstract

Abstract The DOK1 (Downstream of Tyrosine kinase 1) gene is a putative tumor suppressor gene located on human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. The DOK1 protein is a member of the Dok protein family comprising seven members. It inhibits MAP kinase activity and displays anti-proliferative activities. The DOK1 gene may act as a tumor suppressor gene in ovarian cancer, Burkitt lymphoma, head and neck cancer (HNC), chronic lymphocytic leukaemia (CLL) and lung cancer by inhibiting cell proliferation. So far there is no study in the literature analyzing the relationship between the DOK1 gene and breast cancer. The aim of this study was to investigate the role of the DOK1 gene in breast cancer. The tumors and adjacent normal tissues were collected from 50 patients who underwent surgery for breast cancer at the Bezmialem Vakif University Medical Faculty. For expression analysis, after isolation of RNA cDNA was been obtained. Gene expression levels in the tumors and adjacent normal tissues were determined by quantitative RT-PCR using the 2-ΔΔCT method. The results were normalized using the G6PD gene as reference. For mutation analysis, DNA was isolated and analyzed by cycle sequencing to detect mutations. The SPSS 21.0 software package was used for statistical analysis. P<0.05 was considered significant. When the DOK1 expression levels in the tumors and adjacent normal tissues were compared we observed that DOK1 expression was decreased in 31 (62%) patients and increased in 16 (32%) patients. The decrease of DOK1 expression was associated with age (p=0.031), menopausal status (p=0.017), histologic type, (p=0.015) and stage (p=0.017). We identified 11 different alterations in the non-coding regions of the gene. One of these alterations was in the 5'-UTR and the remaining 10 were located in the introns 1 and 4. We did not observe any significant association between the mutations and expression level of the DOK1 gene. Our results, suggest that the DOK1 gene might act as a tumor suppressor in breast cancer. Citation Format: Nur Buyru, Esin Tuna, Filiz Ozdemir, Pelin Bulut, Nejat Dalay. DOK1 gene may act as a tumor suppressor in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A60.