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Familial Cancer

, Volume 14, Issue 1, pp 69–75 | Cite as

Identification of a novel MSH6 germline variant in a family with multiple gastro-intestinal malignancies by next generation sequencing

  • Ashton A. Connor
  • Hagit Katzov-Eckert
  • Thomas Whelan
  • Melyssa Aronson
  • Lynette Lau
  • Christian Marshall
  • George S. Charames
  • Aaron Pollett
  • Steven Gallinger
  • Jordan Lerner-Ellis
Original Article

Abstract

The identification of germline variants that predispose to cancer is important to further our understanding of tumorigenesis, guide patient management, prevent disease in unaffected relatives, and inform best practice for health care. We describe a kindred with multiple gastrointestinal malignancies where a novel MSH6 germline susceptibility variant was identified by exome sequencing after eluding serial routine testing in multiple affected members. This case fosters discussion of our current understanding of DNA mismatch repair deficiency, the management of Lynch Syndrome, and the emerging role of next generation sequencing in laboratory medicine to identify rare pathogenic germline variants in a comprehensive, unbiased fashion.

Keywords

Gastrointestinal cancer DNA mismatch repair MSH6 Next generation sequencing Clinical genomics 

Notes

Acknowledgments

This study was supported by a McLaughlin Accelerator Grant and by funding from the GeneCure Foundation and the Canadian Institute for Health Research.

Conflicts of interests

We have no financial or personal conflicts of interests to declare.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Ashton A. Connor
    • 1
    • 2
    • 3
    • 4
  • Hagit Katzov-Eckert
    • 1
  • Thomas Whelan
    • 1
  • Melyssa Aronson
    • 1
    • 5
  • Lynette Lau
    • 6
  • Christian Marshall
    • 6
    • 7
  • George S. Charames
    • 8
    • 9
  • Aaron Pollett
    • 8
    • 9
  • Steven Gallinger
    • 1
    • 2
    • 3
    • 4
    • 5
  • Jordan Lerner-Ellis
    • 4
    • 8
    • 9
  1. 1.Lunenfeld-Tanenbaum Research InstituteMount Sinai HospitalTorontoCanada
  2. 2.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  3. 3.Division of General Surgery, Department of SurgeryUniversity of TorontoTorontoCanada
  4. 4.Ontario Institute for Cancer ResearchTorontoCanada
  5. 5.Zane Cohen Centre for Digestive DiseasesMount Sinai HospitalTorontoCanada
  6. 6.The Centre for Applied Genomics, The Hospital for Sick ChildrenPeter Gilgan Centre for Research and LearningTorontoCanada
  7. 7.The McLaughlin CentreUniversity of TorontoTorontoCanada
  8. 8.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  9. 9.Department of Pathology and Laboratory MedicineMount Sinai HospitalTorontoCanada

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