TY - JOUR
T1 - Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma
AU - Borkosky, Silvia S.
AU - Gunduz, Mehmet
AU - Nagatsuka, Hitoshi
AU - Beder, Levent Bekir
AU - Gunduz, Esra
AU - Al Sheikh Ali, Mahmoud
AU - Rodriguez, Andrea P.
AU - Cilek, Mehmet Zeynel
AU - Tominaga, Susumu
AU - Yamanaka, Noboru
AU - Shimizu, Kenji
AU - Nagai, Noriyuki
N1 - Funding Information:
Acknowledgments This work was partially supported by grants-in-aid for scientiWc researches from the Ministry of Education, Culture, Sports, Science and Technology [19592109 (to HN), 18-06262 (to EG), 17406027 (to NN)], Seed Innovation Research from Japan Science and Technology Agency (to MG), from Sumitomo Trust Haragu-chi Memorial Cancer Research Promotion (to MG) and Astrazeneca Research Grant (to MG).
PY - 2009/5
Y1 - 2009/5
N2 - Background: Loss of heterozygosity (LOH) in the ING family members has been shown in head and neck squamous cell carcinoma (HNSCC) except for ING2. Like all the other members of ING family, ING2, which is located at chromosome 4q35.1, is a promising tumor suppressor gene (TSG). In this study, we performed LOH analysis of ING2 in HNSCC and compared it with clinicopathological variables. Materials and methods: We performed LOH analysis in DNAs from 80 paired of normal and HNSCC tissues, using a specifically designed microsatellite marker on chromosome 4q35.1, which detects allelic loss of ING2. TP53 mutation analysis and its relationship with ING2 chromosomal deletion were also performed in available 68 of the samples. The correlation between LOH status and clinicopathological characteristics was evaluated by using statistical methods. The overall survival (OS) and disease free survival (DFS) were also determined. Results: LOH was detected in 54.6% (30/55) of the informative samples. Statistical significance was obtained between LOH and tumor (T) stage (P = 0.02), application of radiotherapy and chemotherapy. Positive node status (N) appeared to be the only independent prognostic factor for both OS (P = 0.031) and DFS (P = 0.044). Conclusions: Our study showed allelic loss of 4q35.1 in HNSCC. The high percentage of LOH suggests ING2 as a candidate TSG in HNSCC. High LOH frequency was statistically associated with advanced T stage, suggesting that ING2 LOH might occur in late stages during HNSCC progression.
AB - Background: Loss of heterozygosity (LOH) in the ING family members has been shown in head and neck squamous cell carcinoma (HNSCC) except for ING2. Like all the other members of ING family, ING2, which is located at chromosome 4q35.1, is a promising tumor suppressor gene (TSG). In this study, we performed LOH analysis of ING2 in HNSCC and compared it with clinicopathological variables. Materials and methods: We performed LOH analysis in DNAs from 80 paired of normal and HNSCC tissues, using a specifically designed microsatellite marker on chromosome 4q35.1, which detects allelic loss of ING2. TP53 mutation analysis and its relationship with ING2 chromosomal deletion were also performed in available 68 of the samples. The correlation between LOH status and clinicopathological characteristics was evaluated by using statistical methods. The overall survival (OS) and disease free survival (DFS) were also determined. Results: LOH was detected in 54.6% (30/55) of the informative samples. Statistical significance was obtained between LOH and tumor (T) stage (P = 0.02), application of radiotherapy and chemotherapy. Positive node status (N) appeared to be the only independent prognostic factor for both OS (P = 0.031) and DFS (P = 0.044). Conclusions: Our study showed allelic loss of 4q35.1 in HNSCC. The high percentage of LOH suggests ING2 as a candidate TSG in HNSCC. High LOH frequency was statistically associated with advanced T stage, suggesting that ING2 LOH might occur in late stages during HNSCC progression.
KW - Chromosome 4q35.1
KW - Head and neck cancer
KW - ING family
KW - ING2
KW - LOH
KW - Tumor suppressor gene
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U2 - 10.1007/s00432-008-0507-y
DO - 10.1007/s00432-008-0507-y
M3 - Article
C2 - 18998165
AN - SCOPUS:63549104401
SN - 0171-5216
VL - 135
SP - 703
EP - 713
JO - Journal of cancer research and clinical oncology
JF - Journal of cancer research and clinical oncology
IS - 5
ER -