POSTER NO: 401

Allelic loss on chromosome 17 in sporadic breast cancer cases characterised for BRCA2 genetic background

Narendra K. Bairwa, R. Bamezai
Jawaharlal Nehru University, New Delhi-110067, India, Human Genetics Section, School of Life Sciences, Jawaharlal Nehru

Familial breast cancer accounts for ~10% of all reported cases; the other 90% are sporadic. Of the 10% familial cases 70% are attributed to mutations in BRCA1 and BRCA2 genes. No single gene, which is crucial for the development of sporadic form of breast cancer, has been identified as yet. Chromosome 17 harbors many putative cancer-causing genes and shows the extensive genetic alterations in sporadic breast cancer cases in cytogenetic studies. In order to explore regions on chromosome 17 for possible susceptible loci, in our preliminary study, we analyzed six polymorphic markers in blood and breast tumor tissue (a pair study) from each cancer patient. Two of these markers were syntenic for 17p13(D17S5, D17S379), the region known to harbor TP53 and BCRP genes, and other four markers covering an area of 22Mb were syntenic for 17q21 (17S855-2.5Mb-D17S93410Mb-D17S787-9Mb-D17S948) region, the region known to harbor BRCA1, PHB and RAD51C genes. The rationale of the study thus was: to establish a low resolution mapping of such a region for alterations, for further fine mapping of susceptible loci in future. Following observations were made: 29.41%(10/34) showed LOH with D17S5, 35.29%(12/34) with D17S379, 40.90%(9/22) with D17S855 (the marker which is intragenic to BRCA1 gene), 57.89% (11/19) with D17S934, 19%(5/26) with D17S787, 31.57% (6/19) with D17S948, markers, respectively. Further, a novel transcribing minisatellite (pBA0.6), located in 17q21 region, reported by us earlier, showed promising results of instability in sporadic breast tumor tissues studied. Overall, the results of this exploratory study of 34 paired samples in patients with sporadic breast tumors will allow us to fine map in future the studied region in order to explore the susceptible loci. Further it will be interesting to study the importance of these allelic imbalances with respect to the markers studied, in the mutational background of the exon 2 of BRCA2 gene and its presence in a heterozygous state in majority of cases studied, and establish clinical relevance of these observations towards the better prognosis and treatment of the disease, in future.(Acknowledgement: The support from DBT to RB for the Project is acknowledged.)