Frequent loss of heterozygosity in chromosomal region 9pter-p13 in tumor biopsies and cytological material of uterine cervical cancer Maria M. Manolaraki a , Demetrios A. Arvanitis a , George Sourvinos a,1 , Stavros Sifakis b , Eugenios Koumantakis b , Demetrios A. Spandidos a, * a Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece b Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Crete, Greece Received 25 June 2001; received in revised form 1 September 2001; accepted 1 September 2001 Abstract Using polymerase chain reaction-based microsatellite analysis we examined 40 cases, tumor biopsies and cytological material, of early stage cervical cancer and 20 healthy donors. Loss of heterozygosity (LOH) was detected in 35 out of 40 cases (87.5%), located on 9pter-p13 (67.5%), 9q32-34 (17.5%), 13q12 (32.5%), 17p13 (0%) and 17q11-q22 (12.5%). Micro- satellite instability (MIN) phenotype was found in three out of 40 cases (7.5%). The accuracy in LOH and MIN detection in cytological material compared to tumor biopsies was 91.5 and 86.0%, respectively. None of the specimens of healthy donors exhibited any genetic alteration. Our data suggest that microsatellite analysis in cytological material could be used for the early detection of cervical cancer. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Microsatellite analysis; Loss of heterozygosity; 9pter-p13; Cervical cancer; Cytological material 1. Introduction Carcinoma of the cervix is one of the most common tumors affecting women world-wide, both in inci- dence and mortality, predominantly in the developing countries, with approximately 500 000 new cases diagnosed annually [1]. The existing diagnostic meth- ods for the early detection of gynecological cancer, such as Pap test, ultrasound examination, cancer biochemical markers, and colposcopical examination of the cervix, are effective for screening women but fail to detect early enough a significant percentage of cervical cancer cases. Although human papilloma- virus (HPV) high-risk types, such as 16, 18, 31, 33, 39, 45, 52, 58, and 69, and infection in the anogenital tract have been characterized as the primary predis- position, additional events are required for cervical cancer development [2]. A common feature of neoplastic cells is genomic instability, due to rapid proliferation or elevated muta- tional rate. The highly polymorphic microsatellite DNA has been extensively used for genetic analysis in various diseases, including neoplasias, as chromo- some mapping tool, as means for the evaluation of DNA integrity or for the identification of novel genes implicated to specific diseases [3,4]. Microsatellite Cancer Letters 176 (2002) 175–181 0304-3835/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3835(01)00750-9 www.elsevier.com/locate/canlet * Corresponding author. Medical School, University of Crete, P.O. Box 1393, Heraklion 71409, Crete, Greece. Tel.: 130-1722- 7809; fax: 130-1725-2922. E-mail address: spandido@hol.gr (D.A. Spandidos). 1 Present address: Department of Virology, University of Glas- gow, Glasgow, UK.