title: Germline mutations of DICER1 in Chinese women with BRCA1/BRCA2-negative familial breast cancer.
abstract: Germline mutations in identified breast cancer susceptibility genes account for less than 20% of Chinese familial breast cancers. Dicer is an essential component of the microRNA-producing machinery; germline mutations of DICER1 have been confirmed in familial pleuropulmonary blastoma, ovarian sex cord-stromal tumors, and other cancers. Low expression of DICER1 is frequently detected in breast cancer. However, whether germline mutations of DICER1 occur in familial breast cancers remain unknown. Sixty-five breast cancer probands from BRCA1/BRCA2-negative Chinese breast cancer families were screened for germline mutations in DICER1. In addition, 100 unrelated healthy females were enrolled as controls. A polymerase chain reaction sequencing assay was used to screen for mutations in coding regions and at the exon-intron boundaries of DICER1. All variants in introns were evaluated using the NNSplice software to determine the potential splicing effect. A total of 12 germline variants were found, including 11 variants in introns and 1 variant in the 3'-non-coding region. Four variants (IVS8-205 C>T, IVS11+131 delGAAA, IVS16+42 delTA, and IVS19+160 T>C) were novel. Three variants (IVS11+105 C>T, IVS16+42 delTA, and 6095 T>A) may affect splice sites. None of the observed variants appeared to be disease-related, suggesting that germline mutations in DICER1 are rare or absent in familial breast cancer patients.
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: W-M
authors.initials: WM
authors.lastname: Cao
authors.affiliation: Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: S-N
authors.initials: SN
authors.lastname: Xie
authors.affiliation: Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Meng
authors.affiliation: Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: W-W
authors.initials: WW
authors.lastname: Ye
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Shao
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China wxiaojia@yahoo.com.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002681:China; D003198:Computer Simulation; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D018202:Pulmonary Blastoma / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D018312:Sex Cord-Gonadal Stromal Tumors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D020033:Protein Isoforms; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases