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Familial Cancer

, Volume 18, Issue 3, pp 343–348 | Cite as

Targeted next generation sequencing screening of Lynch syndrome in Tunisian population

  • Rihab Ben SghaierEmail author
  • Anne Maria Lucia Jansen
  • Ahlem Bdioui
  • Tom Van Wezel
  • Mehdi ksiaa
  • Lamia Elgolli
  • Leila Ben Fatma
  • Slim Ben Ahmed
  • Mohamed Msaddak Azzouz
  • Olfa Hellara
  • Amine Elghali
  • Fathi Darbel
  • Karim Skandrani
  • Moncef Mokkni
  • Ameni Gdissa
  • Rached Ltaief
  • Ali Saad
  • Fahmi Hmila
  • Moez Gribaa
  • Hans Morreau
Original Article
  • 118 Downloads

Abstract

A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients’ tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.

Keywords

Lynch syndrome Tumor Immunohistochemical staining DNA mismatch repair genes MMR panel 

Notes

Acknowledgements

We thank all team members of Human Cytogenetic, Molecular Genetics and Biology of Reproduction laboratory, Farhat HACHED Hospital Sousse-Tunisia, and the Molecular Diagnostics of the Pathology department of the Leiden University Medical Center. Also, we thank all patients and their families for their contribution and great help.

Supplementary material

10689_2019_130_MOESM1_ESM.tif (117 kb)
Supplementary material 1—Presentation of suspected Lynch Syndrome patients tested by NGS. Pedigrees showing candidates with detected variants by MMR Panel and the segregation of the CRC in their families. CRC: Colorectal Carcinoma, BrC: Breast Cancer, Uter: Uterine Cancer, StC: Stomach Cancer, CHC: Hepatocarcinoma, BrnC:Brain Cancer ,LeukC: Leukemia Cancer, LunC:Lung Cancer.Age at diagnosis is mentioned with the type of the cancer; circles represent females; squares represent males; diamonds represent undisclosed gender; cross striped individuals are deceased. Black blocks present patients and family members with CRC, black right upper corner presents family member with Uter cancer, black left upper corners presents family member with StC , black right lower corner presents family member with BrC,black left lower corner presents family member with BrnC, left Black half presents family member with LeukC, right black half presents family member with LunC (TIFF 117 kb)
10689_2019_130_MOESM2_ESM.docx (28 kb)
Supplementary material 2 (DOCX 27 kb)
10689_2019_130_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 15 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Rihab Ben Sghaier
    • 1
    Email author
  • Anne Maria Lucia Jansen
    • 2
  • Ahlem Bdioui
    • 3
  • Tom Van Wezel
    • 2
  • Mehdi ksiaa
    • 4
  • Lamia Elgolli
    • 5
  • Leila Ben Fatma
    • 6
  • Slim Ben Ahmed
    • 6
  • Mohamed Msaddak Azzouz
    • 7
  • Olfa Hellara
    • 8
  • Amine Elghali
    • 9
  • Fathi Darbel
    • 5
  • Karim Skandrani
    • 5
  • Moncef Mokkni
    • 3
  • Ameni Gdissa
    • 1
  • Rached Ltaief
    • 9
  • Ali Saad
    • 1
  • Fahmi Hmila
    • 9
  • Moez Gribaa
    • 1
  • Hans Morreau
    • 2
  1. 1.Cytogenetic, Molecular Genetics and Human Reproduction Biology – Farhat, HACHED HospitalSousseTunisia
  2. 2.Pathology DepartmentLeiden University Medical Centre (LUMC)LeidenThe Netherlands
  3. 3.Cytology and Anatomopathology DepartmentFarhat HACHED HospitalSousseTunisia
  4. 4.Gastroenterology DepartmentSahloul HospitalSousseTunisia
  5. 5.SousseTunisia
  6. 6.Carcinology DepartmentFarhat HACHED HospitalSousseTunisia
  7. 7.Gastroenterology DepartmentMohamed Taahar Maamouri HospitalNabeulTunisia
  8. 8.Gastroenterology DepartmentFatouma Bourguiba HospitalMonastirTunisia
  9. 9.General Surgery DepartmentFarhat HACHED HospitalSousseTunisia

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