TY - JOUR
T1 - Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers
AU - Gunduz, Mehmet
AU - Ouchida, Mamoru
AU - Fukushima, Kunihiro
AU - Ito, Sachio
AU - Jitsumori, Yoshimi
AU - Nakashima, Tomoko
AU - Nagai, Noriyuki
AU - Nishizaki, Kazunori
AU - Shimizu, Kenji
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/6/27
Y1 - 2002/6/27
N2 - 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.
AB - 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.
KW - Head and neck cancer
KW - ING family
KW - ING3
KW - Loss of heterozygosity
KW - Reduced expression
KW - Tumor suppressor gene
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U2 - 10.1038/sj.onc.1205540
DO - 10.1038/sj.onc.1205540
M3 - Article
C2 - 12080476
AN - SCOPUS:0037182760
VL - 21
SP - 4462
EP - 4470
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 28
ER -