Biallelic BRCA2-mutations can cause Fanconi anemia and are found in 
approximately 7% of pancreatic cancers. Recently, several sequence changes in 
FANCC and FANCG were reported in pancreatic cancer. Functional defects in the 
Fanconi pathway can result in a marked hypersensitivity to interstrand 
crosslinking agents, such as mitomycin C. The functional implications of 
mutations in the Fanconi pathway in cancer have not been fully studied yet; 
these studies are needed to pave the way for clinical trials of treatment with 
crosslinking agents of Fanconi-defective cancers. The competence of the proximal 
Fanconi pathway was screened in 21 pancreatic cancer cell lines by an assay of 
Fancd2 monoubiquitination using a Fancd2 immunoblot. The pancreatic cancer cell 
lines Hs766T and PL11 were defective in Fancd2 monoubiquitination. In PL11, this 
defect led to the identification of a large homozygous deletion in FANCC, the 
first cancer cell line found to be FANCC-null. The Fanconi-defective cell lines 
Hs766T, PL11, and CAPAN1 were hypersensitive to the crosslinking agent mitomycin 
C and some to cis-platin, as measured by cell survival assays and G(2)/M 
cell-cycle arrest. These results support the practical exploration of 
crosslinking agents for non-Fanconi anemia patients that have tumors defective 
in the Fanconi pathway.