Premium
Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions
Author(s) -
SanchezCespedes Montserrat,
Okami Kenji,
Cairns Paul,
Sidransky David
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200003)27:3<319::aid-gcc13>3.0.co;2-p
Subject(s) - loss of heterozygosity , biology , tumor suppressor gene , cancer research , head and neck squamous cell carcinoma , gene , primary tumor , gene duplication , cancer , carcinogenesis , genetics , head and neck cancer , allele , metastasis
The candidate tumor‐suppressor gene ING1 encodes p33 ING1 , a nuclear protein which physically interacts with TP53. It has been shown that p33 ING1 acts in the same biochemical pathway as TP53, leading to cell growth inhibition. Interestingly, a rearrangement of the ING1 gene was found in a neuroblastoma cell line, supporting its involvement in tumor development. Because ING1 resides on the long arm of chromosome 13 (13q34) (a region frequently deleted in many tumor types), we sought to characterize its role in head and neck squamous‐cell carcinoma (HNSCC). We first analyzed 44 primary tumors for loss of heterozygosity (LOH) at 13q, using four widely spaced microsatellite markers (13q14, 13q14.3–q22, 13q22, and 13q34). Twenty (48%) of the tumor samples showed LOH in all of the informative markers tested, including D13S1315 at 13q34. Two of the tumors displayed partial losses restricted to one marker (D13S118 at 13q14 in tumor 1164, and D13S135 at 13q14.3–q22 in tumor 1398). We then determined the genomic structure of the ING1 gene and sequenced the entire coding region in 20 primary tumors showing 13q LOH and in five head and neck cancer cell lines. A single germline polymorphism was detected in 10 of the tumors analyzed (T to C change) located 110 nucleotides upstream of the starting methionine. No somatic mutations were found in any of the samples, suggesting that ING1 is not a tumor suppressor gene target in head and neck cancer. Genes Chromosomes Cancer 27:319–322, 2000. © 2000 Wiley‐Liss, Inc.