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No evidence for the role of somatic mutations and promoter hypermethylation of FH gene in the tumorigenesis of nonsyndromic uterine leiomyomas

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Tumor Biology

Abstract

Fumarate hydratase (FH) gene is reported to have specific involvement in syndromic uterine tumors, but its role in nonsyndromic forms is still unclear. Hence, the present study has aimed to screen the role of promoter methylation status and mutations in exon 2 and 7 regions of FH gene in the genesis of nonsyndromic uterine leiomyomas. Leiomyoma and myometrium tissues were collected from 85 hysterectomized uterine specimens. DNA from each of the biopsy was subjected to PCR, methylation-specific restriction assay, and DNA sequencing. In silico analysis was carried out to identify the impact of sequence variants on the protein structure. Chi-square (χ 2) test was used to compare the promoter methylation proportions of leiomyoma and myometrium tissues. No sequence variants were observed in exon 2 region, but three novel heterozygous germ line sequence variants, i.e., c.1010A > C, c.1021 G > A, and c.1066 T > C in exon 7 region of the FH gene were detected in 14/85 (16.5 %) of the cases examined. In silico analysis results showed that c.1010A > C and c.1021 G > A mutations damage the structure and function of FH, whereas c.1066 T > C mutation is mostly tolerant or neutral. No significant difference of FH promoter methylation status between the leiomyoma (11.76 %) and myometrium (5.88 %) tissues was observed (P = 0.176). Therefore, it is concluded that somatic mutations in FH do not show pronounced effect in nonsyndromic uterine leiomyomas compared to that of their syndromic counterparts. However, higher frequency of FH mutations in leiomyoma cases raises the need to conduct larger number of prospective case-control and family-based studies to assess them as risk markers to nonsyndromic leiomyomas.

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Acknowledgments

Funding for this work was granted by the Department of Biotechnology, Government of India (BT /PR/5516/MED/14 /646/2004). Authors deeply thank all the medical staff and study subjects involved in this study. Authors sincerely acknowledge Tariq Masoodi of King Saud University for his help in bioinformatic analysis of sequence variants.

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Authors and Affiliations

  1. Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, 500 004, Andhra Pradesh, India

    Sireesha Vaidya, Noor Ahmad Shaik, Madhavi Latha, Srinivas Chava, Khaliq Mohiuddin, Vijaya Lakshmi Kodati & Qurratulain Hasan

  2. Department of Genetics and Molecular Medicine, Kamineni Hospitals, L.B.Nagar, Hyderabad, 500 068, Andhra Pradesh, India

    Qurratulain Hasan

  3. Department Of Gynecology, Gandhi Hospital, Hyderabad, 500 00, Andhra Pradesh, India

    Annapurna Yalla

  4. Department of Genetics, University College of Science, Osmania University, Hyderabad, 500 007, Andhra Pradesh, India

    Sireesha Vaidya & Kaipa Prabhakar Rao

  5. Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia

    Noor Ahmad Shaik

  6. RAS Life Sciences Pvt Ltd, Hyderabad, 500 076, Andhra Pradesh, India

    Kaipa Prabhakar Rao

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  1. Sireesha Vaidya
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Correspondence to Qurratulain Hasan.

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Vaidya, S., Shaik, N.A., Latha, M. et al. No evidence for the role of somatic mutations and promoter hypermethylation of FH gene in the tumorigenesis of nonsyndromic uterine leiomyomas. Tumor Biol. 33, 1411–1418 (2012). https://doi.org/10.1007/s13277-012-0391-6

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  • DOI: https://doi.org/10.1007/s13277-012-0391-6

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