Detailed deletion mapping on the short arm of chromosome-3 in nasopharyngeal carcinomas

Allelic loss on the short arm of chromosome 3 is one of the most consistent molecular genetic alterations observed in primary nasopharyngeal carcinoma (NPC). Detailed mapping of the region of common deletion on chromosome 3p will help to locate the site of candidate tumor suppressor gene(s) involved in the pathogenesis of NPC. We have examined allelic deletion in 27 primary undifferentiated NPC at 11 chromosomal loci (spanning from 3p13-3p25) using microsatellite polymorphic markers. Allelic loss was observed in 18 of 27 primary tumors (67%) when comparing tumor DNA with normal constitutional DNA of the same patient. Among these 18 cases, 10 showed allelic loss in all informative loci of chromosome 3p and 8 showed partial or interstitial deletion, The highest frequency of allelic loss was found in three loci, D3S1038 (52%), D3S1228 (50%) and D3S659 (50%). In 5 of the 8 cases with partial deletion of chromosome 3p, a common deletion region within 3p13 to 3p14.3, flanked by two loci, D3S1079 (3p13) proximally and D3S1228 (3p14.1-14.3) distally, was identified. These results suggest strongly the presence of tumor suppressor gene(s) within the 3p13 to 3p14.3 region, the deletion of which represent a critical event in the development of NPC. In the remaining 3 cases with partial chromosomal deletion, the pattern of allelic loss suggests the presence of two other regions of deletion distal to the commonly deleted region (3p13-14.3) identified. The presence of multiple deleted regions on chromosome 3p in NPC suggests that more than one tumor suppressor gene on 3p may be involved in the development of NPC.