Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.
Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been reported. However, tumor-suppressor genes that may account for the frequent LOH remain to be identified. Recently, one systematic study of genomic sequencing was performed on breast and colorectal cancers and 189 candidate cancer genes (CAN-genes) were reported. Among those CAN-genes, 13 genes are located on chromosome 3p. To investigate whether any of the 13 CAN-genes on chromosome 3p is relevant to HNSCC tumorigenesis, we examined their mutational profiles in eight HNSCC cell lines and 12 tumor-normal pairs of human HNSCC in this study. Three of the 13 CAN-genes, ALS2CL, EPHA3, and CMYA1, each was found to harbor a missense mutation (1/20, 5% for each of the three genes). The mutations appeared hemizygous and SNP array analyses showed that these missense mutations are accompanied by LOH on the remaining allele. In summary, our data offer further support that ALS2CL, EPHA3, and CMYA1 are bona-fide tumor-suppressor genes and contribute to the tumorigenesis of HNSCC. Our data suggest that multiple tumor-suppressor genes are likely to be involved in accounting for the high LOH on chromosome 3p in HNSCC.
Lee
Dong Jin
DJ
The Department of Otolaryngology and Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Schönleben
Frank
F
Banuchi
Victoria E
VE
Qiu
Wanglong
W
Close
Lanny G
LG
Assaad
Adel M
AM
Su
Gloria H
GH
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D036121:Receptor, EphA3; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493234:ALS2CL protein, human; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C512114:XIRP1 protein, human; C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3