Secondary genetic changes in mutated BRCA2 in cisplatin-resistant clones of a pancreatic cancer cell line, Capan-1
(Full-length blots are presented in Supplemental Figure 9) a, Seven Capan-1 clones indicated with a single asterisk (*) restored apparently full-length BRCA2 protein expression. Cell lysates from indicated cells were immunoblotted with BRCA2 antibodies (Ab-1 and Ab-2). A double asterisk (**) indicates a band presumed to be nonspecific. b, Schematic presentation of BRCA2 proteins encoded by transcripts in Capan-1 clones. In all of the BRCA2-restored Capan-1 clones, additional genetic changes in exon 11 of BRCA2 were detected (Table S1, Figs. S4 and S5). All of these secondary genetic changes (shown as white arrow heads or black horizontal bars) cancel the frameshift caused by the original mutation (6174delT, black arrow heads), and the encoded BRCA2 proteins have intact C-terminal regions containing a single strand DNA (ssDNA) binding domain and nuclear localization signals (NLS).