ORIGINAL PAPER Allelic loss of 6q25-27, the PARKIN tumor suppressor gene locus, in cervical carcinoma S. J. Mehdi • M. S. Alam • S. Batra • M. M. A. Rizvi Received: 16 June 2010 / Accepted: 9 July 2010 / Published online: 22 July 2010 Ó Springer Science+Business Media, LLC 2010 Abstract Studies on loss of heterozygosity have been made for Parkin gene-specific microsatellite markers in malignancies like breast, ovary and lungs, and the results have shown a significant association. However, till date, there is no study with respect to Parkin gene-associated microsatellite markers in cervical cancer. The present study deals with the Parkin gene-associated microsatellite markers and the occurrence of its loss of heterozygosity in patients with human cervical cancer. DNA was isolated from the 105 cervical carcinoma samples and matched control specimens. Polymerase chain reaction was per- formed using primer specific for two intragenic markers D6S1599 and D6S305 present in Parkin introns 2 and 7, respectively, and one marker (D6S1008) at telomeric end and further electrophoresed on 8% denaturing polyacryl- amide gel. Overall, 59 of 105 (56%) samples showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 25% (D6S1008) to 48% (D6S305). Chi-square test was performed, and loss of heterozygosity was found significantly higher in both the intragenic markers (D6S1599 and D6S305) when com- pared with the locus at telomeric end (D6S1008) with P \ 0.05. These data argue that Parkin is a tumor sup- pressor gene whose inactivation may play an important role in the carcinoma of uterine cervix. Keywords Cervical cancer Á Parkin Á Loss of Heterozygosity Á Tumor Suppressor Gene Introduction The process of carcinogenesis is thought to occur as a stepwise accumulation of genetic alterations, which mainly includes activation of oncogenes and inactivation of tumor suppressor genes [1]. The mechanisms by which tumor suppressor genes contribute to the establishment and/or progression of tumor involve the loss or inactivation of their wild-type alleles. Detection of this loss of somatic alleles (LOH) in the tumor DNA of cancer-affected indi- viduals has been possible through the use of microsatellite markers [2]. Frequent loss of heterozygosity (LOH) in a chromosomal region is considered to be an indicator for harboring a putative tumor suppressor gene [3]. From several LOH studies, chromosome 6q have been reported in the pathogenesis of a number of human malig- nancies, including breast carcinoma [4], malignant melanoma [5], renal cell carcinoma [6], salivary gland adenocarcinoma [7], ovarian carcinoma [8], acute lymphoblastic leukemia & nodal non-Hodgkin’s lymphomas [9], gastric carcinoma [10], hepatocellular carcinoma [11], small-cell lung carcinoma [12], prostate carcinoma [13], parathyroid adenoma [14], capillary hemangioblastomas [15], thymoma [16] and cervi- cal cancer [17]. LOH analysis of the long arm of chromosome 6 identified several regions of loss: 6q21-23 [18], 6q25.1- q25.2 [19] and 6q 25-27 [20, 21]. Moreover, deletions at 6q27 are present in benign ovarian tumors [22], suggesting that alterations in one or more genes mapped on this region rep- resent an early event in ovarian tumorigenesis. Human cervix cancer is an important public health problem. Cervix cancer is the seventh in frequency overall, S. J. Mehdi Á M. S. Alam Á M. M. A. Rizvi (&) Genome Biology Lab., Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India e-mail: rizvijmi@gmail.com S. Batra Department of Gynecology and Obstetrics, LNJP Hospital, New Delhi 110002, India 123 Med Oncol (2011) 28:1520–1526 DOI 10.1007/s12032-010-9633-x