title: A novel PALB2 truncating mutation in an Italian family with male breast cancer.
abstract: Male breast cancer (MBC) is a rare disease, accounting for ~1% of all breast cancer cases worldwide. Although other genes are also involved, predisposing genetic factors to MBC include germline mutations in the BRCA genes (BRCA2). Among the other genes, partner and localizer of BRCA2 (PALB2) is considered a moderate-penetrance breast cancer susceptibility gene that may also play a role in MBC predisposition. Thus, the aim of the present study was to determine the PALB2 gene status in 8 MBC cases selected from a cohort of 181 hereditary breast and/or ovarian cancer probands. We performed PALB2 mutational analysis by direct sequencing of 13 exons and adjacent intronic regions. This study showed the presence of a PALB2 truncating mutation in 1/8 (12.5%) cases. This novel mutation was named c.1285_1286delAinsTC (p.I429SfsX12) and is localized in exon 4 of PALB2, in the region encoding for the ChAM motif which is important for the efficient association of PALB2 to chromatin and for recruitment of the BRCA complex to accumulate RAD51 at double-strand break sites. Our findings indicate that PALB2 could be added to the list of breast cancer susceptibility genes also in families with MBC cases.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vietri
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Caliendo
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Casamassimi
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: De Paola
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Molinari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000235:genetics; D001483:Base Sequence; D018567:Breast Neoplasms, Male / Q000235:genetics*; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; C551750:BRCA2 protein, human; C512790:PALB2 protein, human; C508053:ERBB2 protein, human