Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer.
BACKGROUND
The genetic basis of susceptibility to prostate cancer (PRCA) remains elusive. Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases. 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. This functional relationship made PALB2 a candidate PRCA susceptibility gene.


METHODS
We sequenced PALB2 in probands from 95 PRCA families, 77 of which had two or more cases of early onset PRCA (age at diagnosis <55 years), and the remaining 18 had one case of early onset PRCA and five or more total cases of PRCA.


RESULTS
Two previously unreported variants, K18R and V925L were identified, neither of which is in a known PALB2 functional domain and both of which are unlikely to be pathogenic. No truncating mutations were identified.


CONCLUSIONS
These results indicate that deleterious PALB2 mutations are unlikely to play a significant role in hereditary prostate cancer.
Tischkowitz
Marc
M
Program in Cancer Genetics, Department of Oncology, McGill University, Montréal, QC, Canada.
Sabbaghian
Nelly
N
Ray
Anna M
AM
Lange
Ethan M
EM
Foulkes
William D
WD
Cooney
Kathleen A
KA
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000076164:Fanconi Anemia Complementation Group N Protein; D005220:Fathers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D017422:Sequence Analysis, DNA; D035781:Siblings; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins