Abstract P2-03-19: Discovery of the genes that underpin the transition to malignant phenotype of breast tumors in highly consanguineous region

Abstract

Abstract Breast cancer (BC), a multifactorial and heterogeneous disease is a predominant women form of cancer worldwide affecting 22.9%. The rationale of this study is based on the following observations: 1) in Oman, a significantly increasing number of younger females (25-40 years) present to the clinic with advanced stage of BC; 2) in Oman, the rate of consanguinity is significantly high (52%); and 3) the transition from normal/begnin to malignant phenotype of breast tumor requires the involvement of a subset of specific genes. The long-term objective of this study is to identify and validate the subset of genes that are responsible for this malignant transformation using functional genomic studies, focus on this young age group of patients attending BC clinic (sporadic and familial). RNA samples were isolated from 40 Breast Tumors and 40 Normal tissues and analyzed by Microarray Gene Expression Profiling. Among a number of genes that were up and down regulated, BRIP1, HOXB3 and MAGED1 were identified as potential genes that might underpin the transition to the malignant phenotype; these genes were validated by RT-PCR using the same RNA samples that were examined by microarray. Pathway analysis was carried out to identify the major functional pathways connecting these genes. Ongoing sequencing of these genes using DNA extracted from the same samples will ultimately identify any genetic alteration that can affect the normal function of these genes. Functional validation assays aim to validate further the physiological relevance of these genes in tumor malignancy, and perhaps other novel genes specific to BC in the Omani population. Identification and validation of these genes will potentially pave the way towards the design of anti-cancer therapeutic strategies. Citation Format: Ishita Gupta, Allal Ouhtit, Somya Shanmuganathan, Hamad Al-Riyami. Discovery of the genes that underpin the transition to malignant phenotype of breast tumors in highly consanguineous region [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-19.