Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation‐dependent probe amplification

Abstract

Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation‐dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin‐fixed paraffin‐embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5–8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC.

Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer

“…The alterations most frequently found in the present study were deletions (17%), despite the fact that point mutations are reported as the most common. Similar to the present study, several studies (in different tumours) also have found p53 gene deletions ranging from 8 to 25% (24)(25)(26). We observed deletions in only one allele, localized in exons 5-6 of p53 gene.…”

Coexistence of YWHAZ amplification predicts better prognosis in muscle-invasive bladder cancer with CDKN2A or TP53 loss

“…The mutation or deletion of TP53 gene is commonly seen in bladder cancer patients [9]. In our cohort, TP53 mutation or deletion is seen in 52% of the patients.…”

Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis

“…Although researchers have made some progress in Fig. 7 Schematic summary of the mechanism by which circGLIS3 promotes the proliferation of bladder cancer cells the study of bladder cancer, such as identifying a wide variety of tumor markers and therapeutic targets (Bazrafshani et al 2016;Noel et al 2015;Puntoni et al 2016;Onal et al 2015), the treatment of bladder cancer is still not optimistic. Therefore, new and effective tumor markers and drug targets are urgently needed to support clinical diagnosis and treatment, and research into novel target molecules is extremely important.…”