DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 56; no. 11; pp. 2519 - 2521
• Main Authors: SE KYU KIM, FAN, Y, PAPADIMITRAKOPOULOU, V, CLAYMAN, G, HITTELMAN, W. N, WAUN KI HONG, LOTAN, R, MAO, L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.1996
• Subjects: Base Sequence; Biological and medical sciences; Carcinoma, Squamous Cell - genetics; Chromosomes, Human, Pair 18; DNA Primers - chemistry; DNA-Binding Proteins; Genes, Tumor Suppressor; Genetic Markers; Head and Neck Neoplasms - genetics; Heterozygote; Humans; Medical sciences; Microsatellite Repeats; Molecular Sequence Data; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Proteins - genetics; Sequence Deletion; Smad4 Protein; Trans-Activators; Tumors; Human; Squamous cell carcinoma; Nonsense mutation; Pathogenesis; Heterozygosity loss; Malignant tumor; Tissue; Chromosome E18; Established cell line; Head and neck; ENT disease; Tumor cell; Tumor suppressor gene
• ISSN: 0008-5472

DPC4, a candidate tumor suppressor gene, was identified recently at chromosome 18q21.1. Frequent homozygous deletion or mutations of the gene were observed in pancreatic carcinomas. To investigate the role of this gene in head and neck squamous cell carcinomas (HNSCCs), we examined 16 HNSCC cell lines from 11 patients and 20 primary HNSCCs for alterations of the gene by sequencing all 11 exons of the gene. Fourteen cell lines from 10 patients showed monomers at marker D18s46 (l8q21.1). Full-length cDNA was detectable in all cell lines by reverse transcription-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 patient. Loss of heterozygosity was found in 7 of 15 (47%) informative primary tumors at D18s46, whereas only one polymorphism was observed in both tumor and normal tissues from the same patient (at codon 525; ATT to GTT, isoleucine to valine). Our data indicate that although DPC4 is altered infrequently in HNSCC, it may play some role in the tumorigenesis of a small subset of HNSCCs.