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Identification of Genetic Variants in Exon 4 of TP53 in Lung Carcinoma and in Silico Prediction of Their Significance

  • ORIGINAL RESEARCH ARTICLE
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Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Lung cancer is a severe and the leading cause of cancer related deaths in men and women all over the world. Tumor suppressor protein (TP53) encoded by the TP53 gene which plays a pivotal role in various cellular tumor suppression processes viz cell cycle arrest and apoptosis. Henceforth, the present study was aimed to TP53 exon4 variants from lung carcinoma. Histopathologic and clinically proven 20 patients of lung cancer were enrolled in this study the average age of patients was 45 ± 8 years which categorized as early onset of lung cancer. Genomic DNA was isolated from the blood specimen of patients. Extracted DNA was subjected to PCR amplification for exon 4 of TP53 using appropriate primers and subsequently amplified products were applied to nucleotide alterations via using the DNA sanger sequencing. The genetic analysis documented five variants in exon4 of TP53 which include viz. 4 substitutions [c.215 > C at codon 72, C. 358–359AA > GG at codon 120] were highly prevalent, occurring in 63% and 25% frequency in patients. Other two variants viz. C. 358 A > C at codon 120, C. 365T > G at codon 122 were present at frequency of 15% whilst one deletion variant [152 del C] was found with 5% frequency. Furthermore, alterations on codon 72, 120,122 and 51 were characterized as possibly damaging by Poly Phen-2 and decreased stability using stability bioinformatic tool. Taken together all these findings infer that TP53 gene involved in modulation and susceptibility to lung cancer.

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Abbreviations

TP53:

Tumor suppressor protein

A:

Adenine

C:

Cytosine

T:

Thymine

G:

Guanine

NSLC:

Non-small lung cancer

LOH:

Loss of heterozygosity

LFS:

Li-Fraumeni syndrome

PCR:

Polymerase chain reaction

CGC:

Arginine

CCC:

Proline

AAG:

Lysine

CAG:

Glutamine

GGG:

Glycine

GTG:

Valine

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Acknowledgements

Authors duly acknowledge M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India.

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Authors and Affiliations

  1. Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, India

    Rajendra Prasad, Kirti Sharma, Karanpreet Bhutani, Suvarna Prasad & Sunita Manhas

  2. Department of Biochemistry, AIIMS, Deoghar, India

    Suvarna Prasad

  3. Department of Respiratory Medicine, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, India

    Jai Kishan

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  1. Rajendra Prasad
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  2. Kirti Sharma
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Correspondence to Rajendra Prasad.

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The study was approved by the ethical Committee of M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India.

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Prasad, R., Sharma, K., Bhutani, K. et al. Identification of Genetic Variants in Exon 4 of TP53 in Lung Carcinoma and in Silico Prediction of Their Significance. Ind J Clin Biochem 39, 276–282 (2024). https://doi.org/10.1007/s12291-022-01099-9

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  • DOI: https://doi.org/10.1007/s12291-022-01099-9

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