Document Detail


Identification of a novel NBN truncating mutation in a family with hereditary prostate cancer.
MedLine Citation:
PMID:  22864661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nibrin (NBN), located on chromosome 8q21 is a gene involved in DNA double-strand break repair that has been implicated in the rare autosomal recessive chromosomal instability syndrome known as Nijmegen Breakage Syndrome (NBS). NBS is characterized by specific physical characteristics (microcephaly and dysmorphic facies), immunodeficiency, and increased risk of malignancy. Individuals who are heterozygous for NBN mutations are clinically asymptomatic, but may display an elevated risk for certain cancers including, but not limited to, ovarian and prostate cancer as well as various lymphoid malignancies. In this study, 94 unrelated familial prostate cancer cases from the University of Michigan Prostate Cancer Genetics Project (n = 54) and Johns Hopkins University (n = 40) were subjected to targeted next-generation sequencing of the exons, including UTRs, of NBN. One individual of European descent, diagnosed with prostate cancer at age 52, was identified to have a heterozygous 2117 C > G mutation in exon 14 of the gene, that results in a premature stop at codon 706 (S706X). Sequencing of germline DNA from additional male relatives showed partial co-segregation of the NBN S706X mutation with prostate cancer. This NBN mutation was not observed among 2768 unrelated European men (1859 with prostate cancer and 909 controls). NBN is involved in double-strand break repair as a component of the MRE11 (meiotic recombination 11)/RAD50/NBN genomic stability complex. The S706X mutation truncates the protein in a highly conserved region of NBN near the MRE11 binding site, thus suggesting a role for rare NBN mutations in prostate cancer susceptibility.
Authors:
Kimberly A Zuhlke; Anna M Johnson; Linda A Okoth; Elena M Stoffel; Christiane M Robbins; Waibov A Tembe; Claudia A Salinas; S Lilly Zheng; Jianfeng Xu; John D Carpten; Ethan M Lange; William B Isaacs; Kathleen A Cooney
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Familial cancer     Volume:  11     ISSN:  1573-7292     ISO Abbreviation:  Fam. Cancer     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-31     Completed Date:  2013-04-23     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  100898211     Medline TA:  Fam Cancer     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  595-600     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Sequence
Case-Control Studies
Cell Cycle Proteins / genetics*
DNA Primers / chemistry
Female
Genetic Predisposition to Disease*
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation / genetics*
Nuclear Proteins / genetics*
Pedigree
Prognosis
Prostatic Neoplasms / genetics*
Sequence Homology, Amino Acid
Grant Support
ID/Acronym/Agency:
CA136621/CA/NCI NIH HHS; CA79596/CA/NCI NIH HHS; HL-102923/HL/NHLBI NIH HHS; HL-102924/HL/NHLBI NIH HHS; HL-102925/HL/NHLBI NIH HHS; HL-102926/HL/NHLBI NIH HHS; HL-103010/HL/NHLBI NIH HHS; P50 CA069568/CA/NCI NIH HHS; P50 CA69568/CA/NCI NIH HHS; R01 CA079596/CA/NCI NIH HHS; R01 CA136621/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA Primers; 0/NBN protein, human; 0/Nuclear Proteins
Comments/Corrections

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