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DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma
S K Kim1, Y Fan, V Papadimitrakopoulou
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
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.
Insights
The DPC4 tumor suppressor gene, often altered in pancreatic cancer, was investigated in head and neck squamous cell carcinomas (HNSCCs). While infrequently altered, DPC4 mutations may contribute to a small subset of HNSCC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DPC4 is a tumor suppressor gene located at chromosome 18q21.1.
- Frequent homozygous deletions or mutations in DPC4 are observed in pancreatic carcinomas.
- The role of DPC4 in head and neck squamous cell carcinomas (HNSCCs) requires investigation.
Purpose of the Study:
- To investigate alterations of the DPC4 gene in HNSCC.
- To determine the frequency and type of DPC4 gene alterations in HNSCC cell lines and primary tumors.
- To assess the potential role of DPC4 in HNSCC tumorigenesis.
Main Methods:
- Sequencing of all 11 exons of the DPC4 gene.
- Analysis of 16 HNSCC cell lines and 20 primary HNSCCs.
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect full-length cDNA.
- Analysis of loss of heterozygosity at marker D18s46.
Main Results:
- Fourteen cell lines exhibited monomers at marker D18s46.
- Full-length DPC4 cDNA was detectable in all examined cell lines.
- A nonsense mutation was identified in two cell lines (UMSCC22A and UMSCC22B).
- Loss of heterozygosity at D18s46 was found in 47% of informative primary tumors.
- A polymorphism at codon 525 was observed in one patient's tumor and normal tissues.
Conclusions:
- DPC4 gene alterations are infrequent in HNSCC.
- DPC4 may play a role in the tumorigenesis of a small subset of HNSCCs.
- Further research is warranted to fully elucidate the function of DPC4 in HNSCC.