Identification of a novel NBN truncating mutation in a family with hereditary prostate cancer

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)595-600
Number of pages6
JournalFamilial Cancer
Issue number4
StatePublished - Dec 2012


  • Cancer
  • Hereditary
  • NBN gene
  • Prostate

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Genetics(clinical)
  • Cancer Research


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