Romanian Biotechnological Letters Vol. 16, No. 5, 2011 Copyright © 2011 University of Bucharest Printed in Romania. All rights reserved ORIGINAL PAPER 6601 Loss of heterozygosity at the BRCA1 locus in Romanian cancer patients Received for publication, June 25, 2011 Accepted, August 20, 2011 LAURA BUBURUZAN 1‡ , CATALINA LUCA 1‡ , MIHAELA TICA 2 , VALERIA TICA 1 , CAMELIA VRABIE 1 , VLADIMIR BOTNARCIUC 2 , IRINEL POPESCU 3 , MARIETA COSTACHE 1* 1 Department of molecular Biology and Biochemistry, Faculty of Biology, University of Bucharest, 2 Emergency Universitary Hospital of Bucharest, 3 Fundeni Clinical Institute of Bucharest. *Corresponding author: Marieta Costache, Department of Biochemistry and Molecular Biology, Faculty of Biology, Bucharest University, Splaiul Independentei, nr. 91-95, Sector 5, Bucharest, tel. 0731700430, marietacostache@yahoo.com; costache@bio.unibuc.ro ‡ These authors contributed equally to this study. Abstract BRCA1 is a tumor suppressor gene and any alteration of its functions can contribute to cancer development and progression. The loss of heterozigosity (LOH), meaning the loss of the normal functional allele in a heterozygous locus of a tumor suppressor such as BRCA1 gene, leads to wild-type gene inactivation and can be correlated with cancer. The role of BRCA1 LOH has already been demonstrated in familial and sporadic breast cancer. Little is known about BRCA1 LOH correlated with other types of familial cancers such as prostate cancer, esophageal cancer or gastric cancer and even less about BRCA1 LOH correlations with the types of sporadic cancers. The aim of this study was to investigate the correlation between distinct BRCA1 alterations and tumor site or cancer progression in Romanian patients with prostate, esophageal and gastric cancer. For this purpose polymerase chain reaction (PCR)-based microsatellite analysis was used to detect LOH occurring in regions mapping for BRCA1 gene. From all the five analyzed microsatellites, three (D17S855, D17S856 and D17S1322) presented loss of heterozygosity in the DNA extracted from the tumor tissue of different patients. 28% of all analyzed patients, presented loss of heterozygosity of at least one microsatellite marker corresponding to BRCA1 gene locus. Key words. BRCA1 gene, loss of heterozygosity, prostate cancer, esophageal cancer, gastric cancer Introduction BRCA1 (BReast CAncer type 1 gene) is a tumor suppressor gene situated on chromosome 17q21 having a length of 100kb and encoding an 1836 amino acids protein [1,2]. It has been demonstrated that BRCA1 protein plays an important role in cell cycle regulation acting as a tumor suppressor [3]. BRCA1 gene is involved in apoptosis, cell cycle control and genome stability acting upon DNA repair and damage control [4-9]. The role of BRCA1 in DNA repair explains in fact its main function as a tumor suppressor gene. Any alteration of BRCA1 functions can contribute to cancer development and progression. However, the loss of these important and fundamental functions of BRCA1 cannot explain the tissue or gender specificity of cancer risks [10]. Also, sporadic cancer is rarely associated with somatic mutations of BRCA1 which are supposed to be involved in genome instability [11]. BRCA1 was initially correlated with cancer susceptibility by MC King in a study on hereditary breast cancer families [2]. It is shown that mutations in BRCA1 gene are correlated with 50% of the breast cancers and 80-90% of the breast-ovarian cancers [2, 12, 13]. The development and progression of cancer is associated with some events that include alteration of some genes which regulate cell growth and differentiation: activation of oncogenes and inactivation of tumor suppressor genes. This is the reason why the loss of