DPC4, A CANDIDATE TUMOR-SUPPRESSOR GENE, IS ALTERED INFREQUENTLY IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

DPC4, a candidate tumor suppressor gene, was identified recently at ch romosome 18q21.1. Frequent homozygous deletion or mutations of the gen e were observed in pancreatic carcinomas, To investigate the role of t his gene in head and neck squamous cell carcinomas (HNSCCs), we examin ed 16 HNSCC cell lines from 11 patients and 20 primary HNSCCs for alte rations of the gene by sequencing all 11 exons of the gene, Fourteen c ell lines from 10 patients showed monomers at marker D18s46 (18q21.1). Full-length cDNA was detectable in all cell lines by reverse transcri ption-PCR. A nonsense mutation was identified at codon 526 (GAA to TAA , glutamine to termination) in two cell lines (UMSCC22A and UMSCC22B) derived from the primary tumor and lymph node metastasis of the same p atient, Loss of heterozygosity was found in 7 of 15 (47%) informative primary tumors at D18s46, whereas only one polymorphism was observed i n both tumor and normal tissues from the same patient (at codon 525; A TT to GTT, isoleucine to valine), Our data indicate that although DPC4 is altered infrequently in HNSCC, it may play some role in the tumori genesis of a small subset of HNSCCs.