SCREENING FOR BRCA2 MUTATION IN EXON 11.2 AND 11.3 IN BREAST/OVARIAN CANCER WOMEN OF MADHYA PRADESH, INDIA: IDENTIFIES NOVEL MUTATIONS

Farah Khan*, Ruchira Chaudhary, Ragini Gothalwal, Jyoti Jain

ABSTRACT

In this study exon 11.2 and 11.3 of BRCA2 gene were analysed on women (N=90) of breast and ovarian cancer of Gwalior region, Madhya Pradesh (India). Direct sequencing was used for identification and confirmation of mutations. Sequences were analyzed for mutation through various computational methods and comparative analysis with reference sequence of BRCA2 gene. Two novel pathogenic heterozygous mutations were detected in exon 11.3 of BRCA2 and none of the cases showed mutation in exon 11.2 of BRCA2 gene. Critical mutations, first one frameshift (c.4878delG) and second one missense (c.4878G>T) were observed in with the frequency of 1.11% in population. The pathogenic effect of mutation in first one is cause of change in amino acid composition of BRCA2 protein due to shift in coding frame and second missense mutation is may be due to structural change in DNA binding domain of BRCA2 protein. Both these mutations were previously not reported in BIC (Breast Cancer Information Core) database.

Keywords: BRCA1, BRCA2, Madhya Pradesh, Breast and Ovarian Cancer,Critical mutation Direct Sequencing.