Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions

The candidate tumor-suppressor gene INGI encodes p33(INGI) a nuclear protei n which physically interacts with TP53. It has been shown that p33(INGI) ac ts in the same biochemical pathway as TP53, leading to cell growth inhibiti on. Interestingly, a rearrangement of the INGI gene was found in a neurobla stoma cell line, supporting its involvement in tumor development. Because I NGI resides on the long arm of chromosome 13 (13q34) (a region frequently d eleted 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 microsate llite markers (13q14, 13q14.3-q22, 13q22, and 13q34). Twenty (48%) of the t umor samples showed LOH in all of the informative markers tested, including D 13S 13 15 at 13q34. Two of the tumors displayed partial losses restricte d to one marker (D13S118 at 13q14 in tumor 1164, and D 13S135 at 13q 14.3-q 22 in tumor 1398). We then determined the genomic structure of the INGI gen e and sequenced the entire coding region in 20 primary tumors showing 13q L OH and in five head and neck cancer cell lines. A single germline polymorph ism was detected in 10 of the tumors analyzed (T to C change) located 110 n ucleotides upstream of the starting methionine. No somatic mutations were f ound in any of the samples, suggesting that INGI is not a tumor suppressor gene target in head and neck cancer. (C) 2000 Wiley-Liss, Inc.