title: PALB2 variants in hereditary and unselected Finnish prostate cancer cases.
abstract: BACKGROUND
  PALB2 1592delT mutation is associated with increased breast cancer and suggestive prostate cancer (PRCA) risk in Finland. In this study we wanted to assess if any other PALB2 variants associate to increased PRCA risk and clinically describe patients with formerly found PALB2 1592delT mutation.
  
  
  METHODS
  Finnish families with two or more PRCA cases (n = 178) and unselected cases (n = 285) with complete clinical data were initially screened for variants in the coding region and splice sites of PALB2. Potentially interesting variants were verified in additional set of unselected cases (n = 463).
  
  
  RESULTS
  From our clinically defined sample set we identified total of six variants in PALB2. No novel variants among Finnish PRCA cases were found. Clinical characteristics of the variant carriers, including the previously described family carrying PALB2 1592delT, revealed a trend towards aggressive disease, which also applied to a few non-familial cases. Hypersensitivity to mitomycin C (MMC) of lymphoblasts from individuals from the family with 1592delT revealed haploinsufficiency among carriers with altered genotype.
  
  
  CONCLUSIONS
  Though any of the detected PALB2 variants do not associate to PRCA in population level in Finland it cannot be ruled out that some of these variants contribute to cancer susceptibility at individual level.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland. Sanna.K.Pakkanen@uta.fi
authors.forename: Sanna
authors.initials: S
authors.lastname: Pakkanen
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Sanna
authors.initials: S
authors.lastname: Siltanen
authors.forename: Mimmi
authors.initials: M
authors.lastname: Patrikainen
authors.forename: Mika P
authors.initials: MP
authors.lastname: Matikainen
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004252:DNA Mutational Analysis; D005190:Family; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005387:Finland; D006801:Humans; D040582:Inheritance Patterns / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D016685:Mitomycin