Next-generation sequencing of a family with a high penetrance of monoclonal gammopathies for the identification of candidate risk alleles

Cancer. 2017 Oct 1;123(19):3701-3708. doi: 10.1002/cncr.30777. Epub 2017 May 23.

Abstract

Background: The authors describe a family with a high penetrance of plasma cell dyscrasias, suggesting inheritance of an autosomal dominant risk allele.

Methods: The authors performed whole-exome sequencing and reported on a combined approach aimed at the identification of causative variants and risk loci, using the wealth of data provided by this approach.

Results: The authors identified gene mutations and single-nucleotide polymorphisms of potential significance, and pinpointed a known risk locus for myeloma as a potential area of transmissible risk in the family.

Conclusions: To the authors' knowledge, the current study is the first to provide a whole-exome sequencing approach to such cases, and a framework analysis that could be applied to further understanding of the inherited risk of developing plasma cell dyscrasias. Cancer 2017;123:3701-3708. © 2017 American Cancer Society.

Keywords: gene mutations; hereditary cancer; multiple myeloma; next-generation sequencing; single-nucleotide polymorphism.

MeSH terms

  • Alleles*
  • Family
  • Female
  • Genome-Wide Association Study
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics
  • Mutation*
  • Paraproteinemias / genetics*
  • Pedigree
  • Penetrance*
  • Polymorphism, Single Nucleotide*
  • Risk