title: Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women.
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.
authors.affiliation: Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7 Sector 39, Noida 201301, India
authors.forename: Md Kausar
authors.initials: MK
authors.lastname: Neyaz
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D001483:Base Sequence; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007194:India; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase