Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers.
Loss of heterozygosity (LOH) has been frequently detected at chromosome 7q31 region in human head and neck squamous cell carcinomas (HNSCC) and many other cancers, suggesting the existence of tumor suppressor genes (TSG). We analysed LOH at 7q31 region in 49 HNSCC by using six polymorphic microsatellite markers and found allelic deletion in 48% (22/46) of the informative cases. We detected two preferentially deleted regions, one is around D7S643 and the other around D7S486. When we redefined the map of 7q31 region according to the contiguous sequences, a recently identified gene, ING3, was found in the proximity of D7S643. ING3 protein harbors the PHD domain highly homologous among ING family proteins, in which we previously found mutations in a related gene, ING1. As only one missense mutation of the ING3 gene was found in HNSCC, we examined the expression level. Reverse-transcription-PCR analysis demonstrated decreased or no expression of ING3 mRNA in 50% of primary tumors as compared with that of matched normal samples. Especially, about 63% of tongue and larynx tumors showed the decrease and a tendency of higher mortality was observed in cases with decreased ING3 expression. All these findings suggest a possibility that the ING3 gene functions as a TSG in a subset of HNSCC.
Gunduz
Mehmet
M
Department of Otolaryngology, Graduate School of Medicine and Dentistry, Okayama University, Shikata 2-5-1, Japan.
Ouchida
Mamoru
M
Fukushima
Kunihiro
K
Ito
Sachio
S
Jitsumori
Yoshimi
Y
Nakashima
Tomoko
T
Nagai
Noriyuki
N
Nishizaki
Kazunori
K
Shimizu
Kenji
K
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins; D006801:Humans; D019656:Loss of Heterozygosity; D008156:Luciferases / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C459806:ING3 protein, human; D011506:Proteins; D012334:RNA, Neoplasm; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D012313:RNA; D008156:Luciferases