Abstract 802: Minimal deleted regions and their clinical significances in oral squamous cell cacinomas

Abstract

Abstract With improvements in technologies, DNA alterations on a genome-wide scale have been successfully evaluated in several human cancers. To determine frequently novel deletion regions in oral squamous cell carcinomas (OSCCs) in Taiwan and regions specifically associated with clinicopathologic parameters and prognoses, the 400 polymorphic microsatellite markers from Applied Biosystems PRISM Linkage Mapping Set-MD10 (PE Biosystems, Foster City, CA) were used to examine 63 male primary tumors. To make sure that tumor tissue samples for genome-wide LOH screening consisted >90% tumor cells, LCM was performed on immunostaining slide using a PixCell laser capture microscope (Arcturus Engineering, Mountain View, CA). For increasing reliability of statistical analysis, only when a microsatellite marker was able to provide LOH information in more than 30% (> 19 cases) of the DNA samples was considered to be a successful allelotyping. Based on this criterion, 276 markers were included for the present study. The mean heterozygosity rate in these 276 microsatellite markers was 70.04%. The percentage of LOH among the markers was ranged from 3.85% (marker D20S171) to 65.52% (marker D18S478) with a mean of 33.63% (SD, 12.28%). Twenty-four markers displayed >50% LOH and chromosome regions at 2p21, 2p11.2, 5p15.1, 5q35.1 and 7q21.13 were novel frequent LOH regions not reported previously in OSCC. In this study, we found that markers with a LOH frequency >35% are likely to show LOHs associated with cancer-specific phenotypes. Therefore, only markers with a LOH frequency >35% (121 markers) were used to examine whether there were associations between LOH and the clinicopathologic parameters, including age, anatomic site, tumor stage and risk factors of oral cancer (cigarette smoking, alcohol drinking and AQ chewing) and construct minimal deleted region (MDR). Thirty-two MDRs were defined and 10 novel MDRs were noted. A loss of MDR c19r2 (19q13.42-19q13.43) was correlated significantly with cigarette smoking and a loss of MDR c14r1 (14q24.2-14q32.12) and c11r1 (11q13.4-11q25) was associated with disease-free survival. A loss of MDR c14r1 and c11r1 was associated with the magnitude of genomic instability estimated by the proportion of loci showing LOH (PLOH) and the degree of chromosomal derangement estimated by the mean fractional allelic loss (FAL) in a tumor. In conclusion, our comprehensive allelotype analyses have unveiled a few MDRs involved in the development of OSCC in Taiwan. These results provide useful clues for identification of putative tumor suppressor genes by fine mapping of the suspected MDRs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 802.