title: A novel germline PALB2 deletion in Polish breast and ovarian cancer patients.
abstract: BACKGROUND
  PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair.
  
  
  METHODS
  Initially, the entire coding sequence of the PALB2 gene with exon/intron boundaries was evaluated by the PCR-SSCP and direct sequencing methods on 70 ovarian carcinomas. Sequence variants of interest were further studied on enlarged groups of ovarian carcinomas (total 339 non-consecutive ovarian carcinomas), blood samples from 334 consecutive sporadic and 648 consecutive familial breast cancer patients, and 1310 healthy controls from central Poland.
  
  
  RESULTS
  Ten types of sequence variants were detected, and among them four novel polymorphisms: c.2996+58T>C in intron 9; c.505C>A (p.L169I), c.618T>G (p.L206L), both in exon 4; and c.2135C>T (A712V) in exon 5 of the PALB2 gene. Another two polymorphisms, c.212-58A>C and c.2014G>C (E672Q) were always detected together, both in cancer (7.5% of patients) and control samples (4.9% of controls, p = 0.2). A novel germline truncating mutation, c.509_510delGA (p.R170fs) was found in exon 4: in 2 of 339 (0.6%) unrelated ovarian cancer patients, in 4 of 648 (0.6%) unrelated familial breast cancer patients, and in 1 of 1310 controls (0.08%, p = 0.1, p = 0.044, respectively). One ovarian cancer patient with the PALB2 mutation had also a germline nonsense mutation of the BRCA2 gene.
  
  
  CONCLUSIONS
  The c.509_510delGA is a novel PALB2 mutation that increases the risk of familial breast cancer. Occurrence of the same PALB2 alteration in seven unrelated women suggests that c.509_510delGA (p.R170fs) is a recurrent mutation for Polish population.
authors.affiliation: Department of Molecular Pathology, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Kluska
authors.forename: Joanna
authors.initials: J
authors.lastname: Moes
authors.forename: Michalina
authors.initials: M
authors.lastname: Dabrowska
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Niwinska
authors.forename: Pawel
authors.initials: P
authors.lastname: Derlatka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Cendrowski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kupryjanczyk
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000556:secondary; D004247:DNA / Q000097:blood / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000556:secondary; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D004247:DNA