Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients

Belinda Austen, Giancarlo Barone, Anne Reiman, Philip J Byrd, Claire Baker, Jane Starczynski, Michael C Nobbs, Raymond P Murphy, Helen Enright, Elijah Chaila, John Quinn, Tatjana Stankovic, Guy Pratt, A Malcolm R Taylor

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0.033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40-1G>C leading to loss of exon 41. We also report a 48-year-old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas.

Original languageEnglish
Pages (from-to)925-933
Number of pages9
JournalBritish Journal of Haematology
Issue number6
Early online date28 Jun 2008
Publication statusPublished - Sept 2008


  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia
  • Ataxia Telangiectasia Mutated Proteins
  • Blotting, Western
  • Cell Cycle Proteins
  • DNA Mutational Analysis
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Female
  • Humans
  • Male
  • Multiple Myeloma
  • Mutation
  • Mutation, Missense
  • Neoplasm Proteins
  • Protein-Serine-Threonine Kinases
  • Retrospective Studies
  • Tumor Suppressor Proteins
  • Case Reports
  • Journal Article
  • Research Support, Non-U.S. Gov't


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