Field effect in oral precancer as assessed by DNA flow cytometry and array‐CGH

Abstract

'Field cancerization' is an accepted model for oral carcinogenesis. So far, genetically altered fields have been just reported in the presence of carcinomas. This study assessed the distant mirror fields (MFs) of oral precancer by DNA high-resolution flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). Five leukoplakias without dysplasia (OLs), seven dysplastic leukoplakias (DOLs), and 12 corresponding visually normal and non-dysplastic MFs were analyzed. DNA aneuploidy (DNA Index, DI ≠ 1) was detected by hr DNA-FCM on DAPI stained nuclei suspensions. The epithelial DNA aneuploid subclones were FCM-sorted to obtain genomic DNA for a-CGH. Mirror fields, OLs, and DOLs showed increasing prevalence of DNA aneuploidy of, respectively, 8%, 20%, and 57%. The average number of chromosome aberrations (Ch-Abs) was 2.8 in MFs, 3 in OLs, and 10.6 in DOLs. MFs relative to OLs and DOLs had average numbers of Ch-Abs, respectively, of 1.8 and 3.6. Ch-Abs were also observed in DNA diploid sublines, and often the same aberrations were observed in both MFs and corresponding OLs/DOLs. DNA aneuploidy and Ch-Abs in MFs, the last ones being mainly gains, indicate an early onset of field effect in oral carcinogenesis.