title: The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives.
abstract: PALB2 has been recently identified as breast cancer susceptibility gene in western populations. To investigate the contribution of PALB2 mutations to Chinese non-BRCA1/BRCA2 hereditary breast cancer, we screened all coding exons and intron-exon boundaries of PALB2 in 360 Chinese women with early-onset breast cancer or affected relatives from five breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Some genetic variants identified in the cases were then studied in 864 normal controls with no personal or family history of breast cancer. Two protein-truncating PALB2 mutations, 751C>T and 1050_1051delAAinsTCT, were identified in three separate families, and 751C>T was a recurrent mutation. Neither of them, however, were present in the controls (P=0.025). All the truncating mutations occurred in exon 4 of PALB2, and there were still three unclassified variants were detected in the same fragment. We found that exon 4 accounted for 44.1% (15/34) of the person-times carrying with any variant in our study. PALB2 mutations were responsible for approximately 1% of Chinese women with early-onset breast cancer and affected relatives. Our results suggested that a detection of exon 4 before the assay of the whole PALB2 gene might be a cost-effective approach to the screening of Chinese population.
authors.affiliation: Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, People's Republic of China.
authors.forename: A-Yong
authors.initials: AY
authors.lastname: Cao
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Ma
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Feng-Xi
authors.initials: FX
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Gen-Hong
authors.initials: GH
authors.lastname: Di
authors.forename: Kun-Wei
authors.initials: KW
authors.lastname: Shen
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Lu
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Luo
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Yuan
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002681:China; D005192:Family Health; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015995:Prevalence; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins