Investigation of p53 Tumor Suppressor Gene Mutations in Patients with a Lung Mass Using Sequence Analysis

Abstract

A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : The p53 tu mo ur sup pres sor ge ne plays an im por tant ro le in the re gu la ti on of cell pro li fe ra ti on. It is lo ca ted on the short arm of the 17th chro mo so me. It has 11 exons and en codes for a tu mor sup pres sor pro te in cal led p53 which is 53kD in we ight and 393 ami no acids in length. This pro te in, a trans crip ti on fac tor, is an im por tant re gu la tor of cell cycle. Up to da te, a num ber of mu ta ti ons (75 % of which are fo und bet we en co don 26 and 332) ha ve be en de tec ted on p53 ge ne. Recent re se arc hes sho wed that lung ne op lasm re sul ting from the mu ta ti ons of p53 ge ne va ri ed bet ween 33% (ade no car ci no ma) and 70% (small cell lung can cer), and it is re por ted that the hot spots were ma inly fo und at the co dons 175, 248, and 273. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : In this study, the exons, exonin tron junc ti ons, and so me in tron re gi ons, which are lo ca ted bet we en exon 4-9 of p53 ge ne, of 24 pati ents who had a sur gi cal ope ra ti on du e to a lung mass we re exa mi ned by au to ma tic DNA se qu en cing in Uni ver sity of Le ip zig. R Re e s su ul lt ts s: : 53 mis sen se and 7 fra mes hift mu ta ti ons we re de tec ted bet we en 4 th and 9 th exons (Co dons 36-318) of 18 samp les among the 24 samp les. Fifty five of the se mu ta ti ons were he te rozy go us, and five of them were ho mozy go us. Si mi larly, 12 mis sen se mu ta ti ons de tec ted as a re sult of the se ri al analy ses of the re gi on bet we en in trons 4-9, and seven of them we re he te rozy gous and 5 we re ho mozy go us. C Co on nc c l lu u s si i o on n: : So me re se arch re gar ding p53 ge ne re por ted that co don 175, 248, and 273 were hot spots and mu ta ti ons were fre qu ent in the se co dons. Ho we ver we ha ve not seen any mu ta ti ons in any of the se co dons in our study. Nuc le o ti de chan ges at the po si ti ons 13432 (5' be gin ning) and 13999 (3' en ding) of 6th in tron, which are very im por tant re gi ons, may re sult in the for ma ti on of an ab nor mal pro te in. We sup po se that ot her nuc le o ti de chan ges are not very im por tant du e to the ir he te rozy go us na tu re and lo ca ti on. K Ke ey y W Wo or rd ds s: : Lung ne op lasms; ge nes, p53; se qu en ce analy sis, DNA Ö ÖZ ZE ET T A Am ma aç ç: : p53 tü mör bas kı la yı cı ge ni hüc re ço ğal ma sı nın dü zen len me sin de önem li rol oy nar. 17. kro mo zo mun kı sa ko lun da yer leş miş tir. 11 ek so nu var dır ve 53 kD ağır lı ğın da ve 393 ami noasit uzun lu ğun da olan p53 şek lin de isim len di ri len bir tü mör bas kı la yı cı ge ni şif re ler. Bir trans krip si yon fak tö rü olan bu pro te in hüc re dön gü sü nün önem li bir dü zen le yi ci si dir. Bu gü ne ka dar p53 ge nin de (%75'i ko don 26 ve 332 ara sın da olan) bir ta kım mu tas yon lar sap tan mış tır. Son za man lar da ya pı lan araş tır ma lar gös ter miş tir ki p53 ge nin de ki mu tas yon lar dan kay nak la nan ak ci ğer kit le le ri %33 (ade...