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Atypical Case of Highly Mutated h-TERT Promoter in Germline Genome from Buccal Mucosa Cancer

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Abstract

Buccal mucosa cancer has an aggressive nature as it rapidly grows and penetrates with high recurrence rate. Strikingly, carcinoma of buccal mucosa is the most common cancer of oral cavity in India. Recently, telomerase and telomere biology have been implicated in the pathogenesis and progression in various cancers via regulation of telomere maintenance by telomerase expression which is controlled by telomerase reverse transcriptase (TERT) promoter. Strikingly, h-TERT promoter mutations have been incriminated in regulation of telomerase gene expression. Here, we present a 35 years old male with intense coughing, short breathlessness and fever since 15 days, was admitted to the pulmonary unit. He was a chronic smoker and gutka user. The cytopathological analysis of gastric aspirate revealed buccal mucosa carcinoma of IV stage. We identified h-TERT promoter mutations in isolated genomic DNA from whole blood using DNA sequencer. Genetic analysis disclosed that h-TERT promoter region was highly mutated in this patient. Identified mutations include C.-248 del G, C.-272 del G, C.-279 del G, C.-331 del G, C.-349 del G, C.-351 del C, C.-360 G > A, C.-362 T > A, C.-371 del T and C.-372 del T. Further, all identified mutations were subjected to predict the pathologic functional consequences using bioinformatics tools viz TFsitescan and CiiiDER which showed either loss or gain of transcription factors binding sites in h-TERT promoter. This is a unique case in which total 9 mutations were observed in h-TERT promoter in a single case. In conclusion, all together these mutations in h-TERT promoter may alter the epigenetics and subsequently the tenacity of binding transcription factors which are of functional significance.

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Abbreviations

TERT:

Telomerase reverse transcriptase

A:

Adenine

C:

Cytosine

T:

Thymine

G:

Guanine

TLC:

Total leukocyte count

Hb:

Hemoglobin

HNSCC:

Head and neck squamous cell carcinomas

GABP:

GA binding protein transcription factor subunit

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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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No funding was received for this work.

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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, Sonia Panchal & Isha Rani

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

    Gaurav Parashar

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

    Jai Kishan

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

    Mini Bhatnagar

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  1. Rajendra Prasad
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  2. Sonia Panchal
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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., Panchal, S., Rani, I. et al. Atypical Case of Highly Mutated h-TERT Promoter in Germline Genome from Buccal Mucosa Cancer. Ind J Clin Biochem 38, 400–404 (2023). https://doi.org/10.1007/s12291-021-01006-8

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  • DOI: https://doi.org/10.1007/s12291-021-01006-8

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