Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas.
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.
Gunduz
Mehmet
M
Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikatacho, Okayama 700-8525, Japan.
Nagatsuka
Hitoshi
H
Demircan
Kadir
K
Gunduz
Esra
E
Cengiz
Beyhan
B
Ouchida
Mamoru
M
Tsujigiwa
Hidetsugu
H
Yamachika
Eiki
E
Fukushima
Kunihiro
K
Beder
Levent
L
Hirohata
Satoshi
S
Ninomiya
Yoshifumi
Y
Nishizaki
Kazunori
K
Shimizu
Kenji
K
Nagai
Noriyuki
N
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*
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins