Frequent c-myc and Int-2 overrepresentations in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a commonly occurring tumor in southern China. Although several causative factors have now been recognized, the genetic basis underlying its tumorigenesis is still unclear. To identify potential chromosomal aberrations for further investigations, comparative genomic hybridization (CGH) analysis was applied to the study of genomic imbalances in 10 NPC biopsy specimens. Before CGH analysis, the tumor cell content within the biopsy specimens was enriched by tissue microdissection, and universal genome amplification was performed on the recovered DNA. Recurrent chromosomal gains were detected on 1q (6 of 10 cases), 2q (5 of 10 cases), 3q (7 of 10 cases), 6p (8 of 10 cases), 6q (5 of 10 cases), 7q11.2 (4 of 10 cases), 8q (6 of 10 cases), 11q13, 12, and 15q (8 of 10 cases each), 17q (6 of 10 cases), and 20q (5 of 10 cases). Common losses were identified on 3p (5 of 10 cases), 9p (5 of 10 cases), 11q14-qter (8 of 10 cases), and 14q (5 of 10 cases). Among these aberrations, 7, 8, and 11 gains were further investigated on a series of NPC tissue samples, by interphase fluorescent in situ hybridization (FISH), for the incidence of alpha-satellites: 7, 8, and 11 c-myc and Int-2. Low-level increases of alpha-satellite 7 (9 of 34 cases; 26.5%), alpha-satellite 8 (15 of 34 cases; 44%), and alpha-satellite 11 (8 of 32 cases; 25%) were detected, whereas high-level copy gains of c-myc (21 of 34 cases; 62%) and Int-2 (26 of 34 cases; 76.5%) were more frequently found. Our series is the first to identify genomic overrepresentations of c-myc and Int-2 in NPC. The high incidence of Int-2 amplifications strongly suggests a role of this proto-oncogene in the pathogenesis of NPC.