Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma.
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.


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.
Borkosky
Silvia S
SS
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama, Japan.
Gunduz
Mehmet
M
Nagatsuka
Hitoshi
H
Beder
Levent Bekir
LB
Gunduz
Esra
E
Ali
Mahmoud A L Sheikh
MA
Rodriguez
Andrea P
AP
Cilek
Mehmet Zeynel
MZ
Tominaga
Susumu
S
Yamanaka
Noboru
N
Shimizu
Kenji
K
Nagai
Noriyuki
N
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging / Q000401:mortality; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D016019:Survival Analysis; D017741:Survivors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins