Assessment of p53 mutations, expression and prognosis in bladder cancer patients from Jordan: Identification of novel deletion mutations in the DNA-binding domain

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F17%3A43913065" target="_blank" >RIV/62156489:43210/17:43913065 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.mgene.2017.01.002" target="_blank" >https://doi.org/10.1016/j.mgene.2017.01.002</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.mgene.2017.01.002" target="_blank" >10.1016/j.mgene.2017.01.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Assessment of p53 mutations, expression and prognosis in bladder cancer patients from Jordan: Identification of novel deletion mutations in the DNA-binding domain

Popis výsledku v původním jazyce

Bladder cancer is the most common cancer of the urinary tract with an estimate of 401,000 new cases diagnosed annually worldwide. In Jordan, bladder cancer accounts for 4.3% of all newly diagnosed cancer cases. Several studies have linked p53 molecular changes to tumor initiation, invasion, metastasis, and chemoresistance. In the present study, we investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in p53. Overexpression of p53 was shown in 22%, 46%, 71% and 25% pTa, pT1, pT2 and pT4 cases, respectively. Additionally, p53 was overexpressed in 19%, 38% and 74% of G1, G2 and G3 cases of bladder cancer, respectively. p53 expression is not significantly associated with the stage or grade of the disease. Mutational analysis of exons 4-8 of p53 identified the following previously reported point mutations R72P (58%), P67T (9%), A159P (0.7%), D185N (28%), G199 V (0.7%), G199E (0.7%), D208N (0.7%), R283P (1.4%). Furthermore, we were able to identify two new deletion mutations located in the DNA-binding domain in two patients. The first mutation was a result of one nucleotide deletion in exon 5 causing a frameshift at codon 115 resulting in a truncated 168 amino acids long p53 protein and the second is a result of a whole codon deletion in exon 6 resulting in a p53 protein missing a valine residue at codon 218. P53 mutations were found to be significantly associated with late stage (pT2-pT4) muscle-invasive bladder tumors. Survival analysis indicates significant differences of overall survival between the patients with the p53 overexpression and those with negative p53 staining (p = 0.0041). Additionally, were able to observe a significant difference of overall survival between p53 mutants and p53 wild-type (p = 0.0062). The present work points to the variable spectrum of TP53 mutations and p53 expression profile in Jordanian patients with bladder cancer and reflects the importance of p53 alterations in predicting poor prognosis of bladder cancer patients.

Název v anglickém jazyce

Assessment of p53 mutations, expression and prognosis in bladder cancer patients from Jordan: Identification of novel deletion mutations in the DNA-binding domain

Popis výsledku anglicky

Bladder cancer is the most common cancer of the urinary tract with an estimate of 401,000 new cases diagnosed annually worldwide. In Jordan, bladder cancer accounts for 4.3% of all newly diagnosed cancer cases. Several studies have linked p53 molecular changes to tumor initiation, invasion, metastasis, and chemoresistance. In the present study, we investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in p53. Overexpression of p53 was shown in 22%, 46%, 71% and 25% pTa, pT1, pT2 and pT4 cases, respectively. Additionally, p53 was overexpressed in 19%, 38% and 74% of G1, G2 and G3 cases of bladder cancer, respectively. p53 expression is not significantly associated with the stage or grade of the disease. Mutational analysis of exons 4-8 of p53 identified the following previously reported point mutations R72P (58%), P67T (9%), A159P (0.7%), D185N (28%), G199 V (0.7%), G199E (0.7%), D208N (0.7%), R283P (1.4%). Furthermore, we were able to identify two new deletion mutations located in the DNA-binding domain in two patients. The first mutation was a result of one nucleotide deletion in exon 5 causing a frameshift at codon 115 resulting in a truncated 168 amino acids long p53 protein and the second is a result of a whole codon deletion in exon 6 resulting in a p53 protein missing a valine residue at codon 218. P53 mutations were found to be significantly associated with late stage (pT2-pT4) muscle-invasive bladder tumors. Survival analysis indicates significant differences of overall survival between the patients with the p53 overexpression and those with negative p53 staining (p = 0.0041). Additionally, were able to observe a significant difference of overall survival between p53 mutants and p53 wild-type (p = 0.0062). The present work points to the variable spectrum of TP53 mutations and p53 expression profile in Jordanian patients with bladder cancer and reflects the importance of p53 alterations in predicting poor prognosis of bladder cancer patients.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Meta Gene

ISSN

2214-5400

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

June

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

33-42

Kód UT WoS článku

000418337000006

EID výsledku v databázi Scopus

2-s2.0-85009844423