title: 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.
authors.affiliation: Genetics Department, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mohammad Reza R
authors.initials: MR
authors.lastname: Bazrafshani
authors.affiliation: Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Pouriaali A
authors.initials: PA
authors.lastname: Nowshadi
authors.affiliation: Department of Pathology, School of Veterinary Pathology, Shahrekord University, Shahrekord, Iran.|Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran.|Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Shirian
authors.affiliation: Department of Cytopathology, Research Center of Dr. Daneshbod Path Lab, Shiraz, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Daneshbod
authors.affiliation: Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nabipour
authors.affiliation: Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Maral
authors.initials: M
authors.lastname: Mokhtari
authors.affiliation: Department of Genetics, Dr. Mohammad-Reza Bazrafshani Lab, Kerman, Iran.
authors.forename: Fatemehsadat
authors.initials: F
authors.lastname: Hosseini
authors.affiliation: Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Dehghan
authors.affiliation: Department of Cytopathology, Research Center of Dr. Daneshbod Path Lab, Shiraz, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Saeedzadeh
authors.affiliation: Department of Pediatrics, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Mosayebi
mesh_terms: D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D021141:Nucleic Acid Amplification Techniques; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Deletion; TP53 gene; duplication; multiplex ligation-dependent probe amplification; transitional cell carcinoma