Familial Cancer

, Volume 17, Issue 2, pp 197–203 | Cite as

Screening for Lynch syndrome in young Saudi colorectal cancer patients using microsatellite instability testing and next generation sequencing

  • Masood Alqahtani
  • Caitlin Edwards
  • Natasha Buzzacott
  • Karen Carpenter
  • Khalid Alsaleh
  • Abdulmalik Alsheikh
  • Waleed Abozeed
  • Miral Mashhour
  • Afnan Almousa
  • Yousef Housawi
  • Shareefa Al Hawwaj
  • Barry Iacopetta
Original Article

Abstract

Individuals with Lynch syndrome (LS) have germline variants in DNA mismatch repair (MMR) genes that confer a greatly increased risk of colorectal cancer (CRC), often at a young age. Identification of these individuals has been shown to increase their survival through improved surveillance. We previously identified 33 high risk cases for LS in the Saudi population by screening for microsatellite instability (MSI) in the tumor DNA of 284 young CRC patients. The aim of the present study was to identify MMR gene variants in this cohort of patients. Peripheral blood DNA was obtained from 13 individuals who were at high risk of LS due to positive MSI status and young age (<60 years at diagnosis). Next generation sequencing, Sanger sequencing and Multiplex Ligation-dependent Probe Amplification were used to screen for germline variants in the MLH1, MSH2, MSH6 and PMS2 MMR genes. These were cross-referenced against several variant databases, including the International Society for Gastrointestinal Hereditary Tumors Incorporated database. Variants with pathogenic or likely pathogenic significance were identified in 8 of the 13 high risk cases (62%), comprising 4 in MLH1 and 4 in MSH2. All carriers had a positive family history for CRC or endometrial cancer. Next generation sequencing is an effective strategy for identifying young CRC patients who are at high risk of LS because of positive MSI status. We estimate that 7% of CRC patients aged <60 years in Saudi Arabia are due to LS, potentially involving around 50 new cases per year.

Keywords

Lynch syndrome Colorectal cancer Microsatellite instability Screening Saudi 

Notes

Acknowledgements

The authors gratefully acknowledge the financial support provided by King Fahad Specialist Hospital-Dammam and the Saudi Arabia Cultural Mission of the Royal Embassy. We also extend our appreciation to Ahmed Alotaibi, Elhassan Khalafaalla, Elhassan Taha, Clara Kutty and the HIL laboratory for their technical support and use of laboratory facilities. The authors are grateful to Dr. Lyn Schofield for helpful discussions.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Masood Alqahtani
    • 1
    • 2
  • Caitlin Edwards
    • 3
  • Natasha Buzzacott
    • 3
  • Karen Carpenter
    • 3
  • Khalid Alsaleh
    • 4
  • Abdulmalik Alsheikh
    • 4
  • Waleed Abozeed
    • 4
    • 5
  • Miral Mashhour
    • 2
  • Afnan Almousa
    • 2
  • Yousef Housawi
    • 2
  • Shareefa Al Hawwaj
    • 2
  • Barry Iacopetta
    • 1
  1. 1.Faculty of Health and Medical Sciences, School of Biomedical SciencesUniversity of Western AustraliaNedlandsAustralia
  2. 2.Department of Pathology and Laboratory Medicine, Department of GeneticsKing Fahad Specialist Hospital-DammamDammamSaudi Arabia
  3. 3.Department of Diagnostic GenomicsPathWestNedlandsAustralia
  4. 4.College of MedicineKing Saud University Medical City, King Saud UniversityRiyadhSaudi Arabia
  5. 5.Clinical Oncology Department, Faculty of MedicineMansoura UniversityMansouraEgypt

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