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Genetic Changes of P53 and Kras in Gallbladder Carcinoma in Kumaon Region of Uttarakhand

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Abstract

Background

Gallbladder carcinoma is a highly lethal but relatively rare neoplasm of the digestive tract. p53 mutations are one of the most frequent genetic alterations in human cancers and are thought to play a role in pathogenesis of several malignancies. Kras oncogene is responsible for high frequency recognized as an early event in pancreatic and colonic carcinogenesis.

Objectives

We investigated the genetic change of p53, Kras and histopathological changes in gallbladder cancer tissue samples.

Methods

P53 mutation was seen in the axons 5, 6, 7 and 8 of p53 gene and Kras codon 12 mutations in 25 operative specimens of gallbladder carcinoma. The hispathology observations and polymerase chain reaction-based techniques of these patients were used for point mutations study in p53 and in codon 12 of Kras gene.

Results

Mutations of p53 analyzed from exons 5 to 8 using the method of PCR-SSCP were 44%, PCR-RFLP was carried out, and incidence of mutation in codon 12 of Kras was 48% in the adenocarcinoma patients. There was a significant correlation between presence of gall stone, histopathological type, cellular differentiation, grade, lymphovascular invasion, perineural invasion, lymph node invasion, involvement of cystic duct end margin, liver invasion, omental tissue invasion, and T.N.M. staging.

Conclusions

Curative surgical resection remains the only effective approach for treatment of GBC. Studies with large number of cases with latest application, next-generation sequencing, DNA microarray, transcriptome analysis, and real-time PCR would help in exploring more targets and better classification of these cancers at genetic level.

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Acknowledgments

I appreciate the supporting staff of Multidisciplinary Research Unit who contributed to this research work. I am thankful to the surgery department faculty and supporting staff for giving patient’s information and gallbladder sample and processing for study. I acknowledge to pathology department for histopathological finding and data collection of gallbladder carcinoma samples and also to Principal, Government Medical College, Haldwani, Nainital, Uttarakhand for the research place for this work in Multidisciplinary Research Unit laboratory.

Funding

The Department of Health and Research, Ministry of Health & Family Welfare, New Delhi, India provided supporting fund.

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Authors and Affiliations

  1. Multidisciplinary Research Unit, Government Medical College, Haldwani, Nainital, Uttarakhand, 263139, India

    Sanjeev Kumar Shukla

  2. Department of Biochemistry, Rajshree Medical Research Institute, Bareilly, Uttar Pradesh, 243501, India

    Govind Singh

  3. Department of Surgery, Government Medical College, Haldwani, Nainital, Uttarakhand, 263139, India

    Kedar Singh Shahi &  Bhuvan

  4. Department of Pathology, Government Medical College, Haldwani, Nainital, Uttarakhand, 263139, India

    Prabhat Pant

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  1. Sanjeev Kumar Shukla
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Contributions

Sanjeev Kumar Shukla helped to draft the manuscript and in the collection and preparation of data, figure, and table. Govind Singh carried out the design of the study, performed the acquisition of data, and approved the final version of the manuscript. Bhuvan and K.S. Shahi provided the positive samples of the gallbladder carcinoma. Prabhat Pant conceived the study and pathological analysis, participated in its design, and helped in sample screening. All the authors read and approved the final manuscript.

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Correspondence to Govind Singh.

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Shukla, S.K., Singh, G., Shahi, K.S. et al. Genetic Changes of P53 and Kras in Gallbladder Carcinoma in Kumaon Region of Uttarakhand. J Gastrointest Canc 51, 552–559 (2020). https://doi.org/10.1007/s12029-019-00283-0

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  • DOI: https://doi.org/10.1007/s12029-019-00283-0

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