Tripathi K, Goel A, Singhai A, Garg M. Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder. World J Clin Oncol 2020; 11(8): 614-628 [PMID: 32879848 DOI: 10.5306/wjco.v11.i8.614]
Corresponding Author of This Article
Minal Garg, MSc, PhD, Assistant Professor, Doctor, Department of Biochemistry, University of Lucknow, University Road, Lucknow 226007, India. minal14@yahoo.com
Research Domain of This Article
Oncology
Article-Type of This Article
Observational Study
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Tripathi K, Goel A, Singhai A, Garg M. Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder. World J Clin Oncol 2020; 11(8): 614-628 [PMID: 32879848 DOI: 10.5306/wjco.v11.i8.614]
Kiran Tripathi, Minal Garg, Department of Biochemistry, University of Lucknow, Lucknow 226007, India
Apul Goel, Department of Urology, King George Medical University, Lucknow 226003, India
Atin Singhai, Department of Pathology, King George Medical University, Lucknow 226003, India
Author contributions: Tripathi K contributed to the conception and design of the study; Tripathi K performed the experiments and participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Goel A and Singhai A revised the article critically for important intellectual content; Garg M contributed to the conception and design of the study and revised the article critically for important intellectual content; all the authors approved the final version of the article to be published.
Supported byDepartment of Science and Technology, Govt. of India, No. SR/SO/HS-0113/2010; University Grants Commission (UGC), Govt. of India; No. 22/12/2013(ii)EU-V.
Institutional review board statement: This study was approved by the appropriate institutional research ethics committee and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Ethical clearance was obtained from Bioethics Cell, Institutional Ethics Committee (IEC), KGMU (Reference no. 89th ECM II A/P8), Lucknow, India.
Informed consent statement: Subjects were not required to give informed consent as the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors of the study declare no potential conflict-of-interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Corresponding author: Minal Garg, MSc, PhD, Assistant Professor, Doctor, Department of Biochemistry, University of Lucknow, University Road, Lucknow 226007, India. minal14@yahoo.com
Received: January 20, 2020 Peer-review started: January 20, 2020 First decision: April 21, 2020 Revised: May 21, 2020 Accepted: July 1, 2020 Article in press: July 1, 2020 Published online: August 24, 2020 Processing time: 213 Days and 12.9 Hours
ARTICLE HIGHLIGHTS
Research background
Mutational activation of Ras genes has been established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.
Research motivation
Due to the reported heterogeneity among the distribution of the most frequent mutations in Ras isoforms in different patient populations with urothelial carcinoma of the bladder (UCB), it is necessary to determine the presence/absence of mutations in order to predict disease outcome.
Research motivation
The present study was conducted to determine the mutational spectrum at the hotspot regions of H-Ras, K-Ras and N-Ras genes.
Research objectives
PCR-RFLP and direct DNA sequencing were employed to determine the presence or absence of mutations in the Ras isoforms and their clinical impact, if any, in 87 UCB patients.
Research methods
None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene; codon 61 of N-Ras gene and codons 12, 13 of K-Ras gene by PCR-RFLP. Direct DNA sequencing of tumor and control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even a single nucleotide difference in the coding exons 1 and 2 of H-Ras, N-Ras and K-Ras genes in the tumor and normal bladder mucosal specimens.
Research results
Our findings on the lack of mutations in H-Ras, K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression, inherent genetic susceptibility, and or tissue specificity in a given cohort of patients.
Research conclusions
Gene amplification and/or overexpression of Ras could further explain an alternative mechanism of its dysfunction in Ras driven cancers.
