Familial Cancer

, Volume 7, Issue 2, pp 151–155 | Cite as

Is MSH2 a breast cancer susceptibility gene?

  • EE Ming Wong
  • Andrea A. Tesoriero
  • Gulietta M. Pupo
  • kConFab
  • Margaret R. E. McCredie
  • Graham G. Giles
  • John L. Hopper
  • Graham J. Mann
  • David E. Goldgar
  • Melissa C. Southey


Mutations in the DNA mismatch repair gene MSH2 lead to increased replication error and microsatellite instability and account for a substantial proportion of hereditary non-polyposis colorectal cancer (Lynch syndrome). A recent international collaborative genome-wide linkage scan (GWS) for breast cancer susceptibility loci found some evidence for there being a breast cancer susceptibility gene in a genomic region on chromosome 2p close to MSH2. We sought to investigate the possibility that mutations in MSH2 might explain the multiple cases of breast cancer in some families that were included in the international GWS. DNA samples from the affected probands of 59 multiple-case breast cancer families, many of whom gave LOD scores >0.5 in the MSH2 region, were screened for large genomic alterations in MSH2 via the Multiplex Ligation-dependant Probe Amplification (MLPA) assay and for coding region mutations via exonic sequencing. Several of the families also contained cases of colorectal cancer in addition to breast cancer and had been included in the GWS that had identified a positive LOD score on chromosome 2p. Using MLPA, c.1236C > T was identified in one proband but this variant was not predicted to create an alternate acceptor/donor site within exon 7 MSH2 using in silico analyses. A c.1734T > C was identified in a second proband via exonic sequencing but testing of the variant in other family members did not support segregation of this variant with disease. Extensive screening of 59 multiple-case breast cancer families did not identify any coding region mutations or larger genomic alterations in MSH2 that might implicate MSH2 as a breast cancer susceptibility gene.


Familial breast cancer Breast cancer susceptibility genes Linkage studies Candidate susceptibility genes MSH2 


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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • EE Ming Wong
    • 1
  • Andrea A. Tesoriero
    • 1
  • Gulietta M. Pupo
    • 2
  • kConFab
    • 3
    • 4
  • Margaret R. E. McCredie
    • 5
  • Graham G. Giles
    • 6
  • John L. Hopper
    • 7
  • Graham J. Mann
    • 2
  • David E. Goldgar
    • 8
  • Melissa C. Southey
    • 1
    • 9
  1. 1.Genetic Epidemiology Laboratory, Department of PathologyThe University of MelbourneMelbourneAustralia
  2. 2.Westmead Institute for Cancer ResearchUniversity of Sydney at Westmead Millennium Institute WestmeadAustralia
  3. 3.Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) c/o the Peter MacCallum Cancer InstituteMelbourneAustralia
  4. 4.The Australian Breast Cancer Family StudyUniversity of MelbourneCarltonAustralia
  5. 5.The University of OtagoDunedinNew Zealand
  6. 6.Cancer Epidemiology CentreCancer Council VictoriaMelbourneAustralia
  7. 7.Centre for Molecular, Environmental, Genetic and Analytic EpidemiologyUniversity of MelbourneMelbourneAustralia
  8. 8.Department of DermatologyUniversity of UtahSalt Lake CityUSA
  9. 9.The International Agency for Research on CancerLyonFrance

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