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Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women

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Abstract

Human papillomavirus (HPV) is considered to be a major etiological factor but is not sufficient for the development of cervical cancer. Other host factors including altered tumor suppressor gene activities might contribute to the carcinogenic process. Fragile Histidine Triad (FHIT) has been shown to play a pivotal role in carcinogenesis. Therefore, we made an attempt to find out point mutation of FHIT gene in HPV mediated cervical cancer in Indian women. 112 cases of cervical carcinoma tissue biopsies and 38 cervical scrapes samples of normal cytology were employed for this study. Herein, we report a novel mutation identified at nucleotide position 655, at codon 98 from CAT → CGT with ultimate replacement of amino acid Histidine by Arginine in cervical cancer cases. Molecular modeling was performed to predict the effect of this mutation in disease pathology. We predict that this change, His to Arg substitution in substrate-binding domain may generate catalytically inactive protein with loss of tumor suppressor activity.

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Acknowledgments

The authors are thankful to Dr. Rajyashri Sharma, Department of Obstetrics and Gynecology, JNMC, Aligarh, for providing clinical samples. This study was done under core fund of ICPO (ICMR), Noida.

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Authors and Affiliations

  1. Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector 39, Noida, 201301, India

    Md. Kausar Neyaz & Mausumi Bharadwaj

  2. Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector 39, Noida, 201301, India

    Showket Hussain & Bhudev C. Das

  3. Centre for Interdisciplinary Research in Basic Sciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India

    Md. Imtaiyaz Hassan

  4. Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi (North Campus), Delhi, 110007, India

    Bhudev C. Das

  5. Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India

    Md. Kausar Neyaz & Syed Akhtar Husain

Authors
  1. Md. Kausar Neyaz
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  2. Showket Hussain
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  3. Md. Imtaiyaz Hassan
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  4. Bhudev C. Das
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  5. Syed Akhtar Husain
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  6. Mausumi Bharadwaj
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Corresponding author

Correspondence to Mausumi Bharadwaj.

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Md. Kausar Neyaz and Showket Hussain contributed equally to this paper.

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Neyaz, M.K., Hussain, S., Hassan, M.I. et al. Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women. Mol Cell Biochem 335, 53–58 (2010). https://doi.org/10.1007/s11010-009-0240-0

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  • DOI: https://doi.org/10.1007/s11010-009-0240-0

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