Novel germline mutations in BRCA2 gene among 96 hereditary breast and breast-ovarian cancer families from Kerala, South India.
OBJECTIVE
Aim of the present study was to identify the genetic heterogeneity, prevalence and frequency of germline mutations of BRCA2 gene in Hereditary Breast/Ovarian cancer patients from Kerala, South India.


METHODS
We analyzed 102 Breast/Ovarian cancer patients from 96 breast and/ovarian cancer families for BRCA2 gene mutations using Conformation-Sensitive Gel Electrophoresis (CSGE) followed by sequencing.


RESULTS
Sequence variations in BRCA2 gene were detected in 27 (26.4%) patients. Sixteen distinct sequence variants were detected of which 11 were (69%) in exon 11. We have identified two novel disease-causing frameshift mutations (c.4642delAA and c.4926insGACC) in two unrelated patients. Apart from this, fourteen distinct sequence variants were detected in 25 breast/ovarian cancer patients of which 8 (57%) were also novel. These include nine missense mutations, one silent mutation, one-nonsense mutation and three intronic variants.


CONCLUSIONS
The results of this study suggest that germline mutations of BRCA2 gene account for rather small proportion of Hereditary Breast/Ovarian cancer in Kerala, South India.
Syamala
Vani
V
Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India. vaniskurup@rediffmail.com
Sreeja
Leelakumari
L
Syamala
Volga S
VS
Vinodkumar
B
B
Raveendran
Praveenkumar B
PB
Sreedharan
Hariharan
H
Kuttappan
Ratheesan
R
Balakrishnan
Lekshmi
L
Ankathil
Ravindran
R
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D015995:Prevalence