title: Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas.
abstract: We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikatacho, Okayama 700-8525, Japan.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gunduz
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
authors.forename: Esra
authors.initials: E
authors.lastname: Gunduz
authors.forename: Beyhan
authors.initials: B
authors.lastname: Cengiz
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamachika
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Levent
authors.initials: L
authors.lastname: Beder
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nishizaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018797:Cell Cycle Proteins; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D020161:Physical Chromosome Mapping / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins