The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.
These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.
Fanconi anaemia (FA) has recently become an attractive model to study breast cancer susceptibility (BRCA) genes, as three FA genes, FANCD1, FANCN and FANCJ, are identical to the BRCA genes BRCA2, PALB2 and BRIP1.
We screened all coding exons of PALB2 in a sample of 50 French-Canadian women diagnosed with either early-onset breast cancer or familial breast cancer at a single Montreal hospital.
Identification in 2002 of the Fanconi anaemia (FA) gene FANCD1 as BRCA2 and recent studies indicating that heterozygous mutations in FANCN/PALB2 and FANCJ/ BRIP1 predispose to breast cancer have emphasised an important connection between the FA and BRCA pathway.
Disease-associated point mutations resulting in protein truncation have been found in BRCA1/2 mutation-negative breast cancer families identifying PALB2 as a susceptibility gene for breast cancer.
PALB2 is a recently identified breast cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures.
We show evidence that PALB2 loss of function might also conform to the inactivation model of a classic tumor-suppressor gene and present data that adds to the clinically relevant discussion about the existence of a PALB2-breast cancer phenotype.
Given the growing evidence now linking BRCA1, BRCA2, and the FA pathway, as well as the involvement of FA proteins (BRCA2/FANCD1 and PALB2/FANCN) in breast cancer susceptibility, we sought to evaluate the contribution of FANCJ gene alterations regarding breast cancer susceptibility among our cohort of 96 breast cancer individuals from high-risk non-BRCA1/2 French Canadian families.
Mutational screening of genes functionally related to BRCA1 and/or BRCA2 has revealed four genes, CHEK2, ATM, BRIP1, and PALB2; mutations in these genes are rare and confer an intermediate risk of breast cancer.
Our results suggest that it may be appropriate to offer PALB2c.1592delT mutation testing to Finnish women with breast cancer, especially those with an early age at onset or a family history of breast or related cancers, and to offer carriers the option of participation in extended disease surveillance programs.
Three of the known FA genes are also high-risk (FANCD1/BRCA2) or moderate-risk (FANCN/PALB2 and FANCJ/BRIP1) breast cancer susceptibility genes, which makes all members of the FA pathway particularly attractive breast cancer candidate genes.
This study supports the recent observation that PALB2 mutation are present, although infrequently, in familial BRCA1/BRCA2-negative breast cancer cases; moreover, it sustains latest evidences that some PALB2 mutations are associated with a substantially increased risk of breast cancer.
Thus, it can be concluded that a predisposing mutation in BRCA1, BRCA2, CHEK2 or PALB2 is present in approximately 6% of French-Canadian women with early-onset breast cancer.
Combined with the results of the former study, our findings further verified that some common PALB2 polymorphisms may contribute to the etiology of breast cancer in Chinese women, so other large studies are warranted to confirm these observations in different ethnic populations.
These include linkage analysis for mapping out BRCA1 and BRCA2, mutational screening of candidate risk genes like CHEK2, ATM, BRIP1 and PALB2, which are associated with an intermediate level of breast cancer risk.
In this study, we evaluated the frequency of PALB21592delT and 229delT mutations in 300 Korean breast cancer patients diagnosed with either familial or early-onset breast cancer.