BRCA2 plays a key role in the maintenance of genomic integrity, particularly through regulation of DNA repair by homologous recombination repair a buy Nilotinib process that is also controlled by another tumour suppressor protein, BRCA1 . HR is a largely error-free process that restores the original sequence at the site of a DNA double-strand breaks . DSBs arise relatively frequently and can be caused by normal cellular replication as well as exogenous stress such as order Doxorubicin exposure to ionising radiation . In the absence of HR, for example due to loss of BRCA2 function, DSBs appear to be repaired by more errorprone processes that ultimately lead to the accumulation of gross chromosomal rearrangements . It is thought that the utilisation of error-prone DNA repair processes in the absence of BRCA2 function most likely fosters tumourigenesis . As part of its role in HR, BRCA2 controls the loading and removal of the DNA recombinase RAD51 at DSBs. The resulting RAD51- ssDNA filament mediates the search for a homologous DNA sequence to template the repair of the DSB . Despite the great interest in BRCA2 function and its role in tumourigenesis and DNA repair, there are few tumour cell models of BRCA2 deficiency that can be used productively in the laboratory. Of these Capan-1 is the most well-characterised. Capan-1 was derived from a liver metastasis in a 40-year-old Caucasian male with a primary pancreatic adenocarcinoma . These cells lack a functional BRCA2 allele and instead carry a c.6174delT allele. The single base deletion at c.6174 causes a frameshift, resulting in loss of the C-terminal 1416 amino acids of the protein . The resultant truncated protein lacks two BRC motifs involved in the interaction between BRCA2 with RAD51 and ssDNA , as well as C-terminal sequences thought to be required for nuclear localization of BRCA2 and RAD51/DNA disassembly . This truncated BRCA2 isoform has been shown to be both cytoplasmic and dysfunctional in HR . In keeping with the concept that BRCA2 dysfunction leads to genomic instability, SKY karyotype analysis has demonstrated that Capan-1 possesses a hypotriploid genome, with 36 defined structural rearrangements distributed across the entire genome . The majority of these rearrangements are likely very complex and appear to involve more than three chromosome segments, although two reciprocal translocations and t ) have been described . Given the considerable use of the Capan-1 cell line as a model not only of BRCA2 dysfunction but also of pancreatic cancer, we used next generation sequencing technology to study the genomic sequence of this cell line.