BACKGROUND: The PALB2 (FANCN) gene was identified as a component of endogenous 
BRCA2 complex that encodes a DNA repair protein participating along with BRCA1 
and BRCA 2 proteins in DNA double-strand break repair. Hereditary PALB2 
mutations are associated with an increased risk of breast and pancreatic cancers 
in heterozygotes. Breast cancer risk for PALB2 mutation carriers has recently 
been estimated at 33-58% depending on family history of breast cancer; 
pancreatic cancer risk in carriers of PALB2 mutations has not been precisely 
quantified, yet.
MATERIALS AND RESULTS: Results of a study identifying PALB2 mutations in 
high-risk, BRCA1/2-negative, breast and/or ovarian cancer patients in the Czech 
Republic indicate that the frequency of hereditary PALB2 mutations in our 
population is quite high. Interestingly, almost 20% of all recognized mutations 
comprised large genomic rearrangements. The highest proportion of PALB2 
mutations (comparable with the number of mutations reported for BRCA2) was found 
in a subgroup of hereditary breast cancer patients (5.5%). Frequency of 
mutations in an independent group of Czech unselected pancreatic cancer patients 
was approximately 1.3%.
CONCLUSION: Considering the frequency of pathogenic, hereditary PALB2 mutations 
in our population, their phenotypic similarity to BRCA2, and expected risk of 
breast cancer associated with PALB2 mutations, its screen-ing (including large 
genomic rearrangements) should be encouraged in patients from hereditary breast 
cancer families. The follow-up of pathogenic PALB2 mutation carriers should be 
similar to that in BRCA2 mutation carriers, enabling early diagnosis, 
prevention, and possible targeted therapy. Preventive surgical interventions for 
the carriers could be considered in case of strong family cancer history and 
evident segregation of a pathogenic mutation with a tumor phenotype. Additional 
analysis of various cancer patient populations and further meta-analyses will be 
necessary for accurate assessment of PALB2 gene penetrance and its significance 
for the risk of pancreatic and other cancers.