Vol.:(0123456789) 1 3 Familial Cancer (2019) 18:343–348 https://doi.org/10.1007/s10689-019-00130-y ORIGINAL ARTICLE Targeted next generation sequencing screening of Lynch syndrome in Tunisian population Rihab Ben Sghaier 1  · 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 Published online: 21 May 2019 © Springer Nature B.V. 2019 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 genera- tion 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-profcient tumors, but with severe family history. In six of 11 patients a ger- mline 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 afect 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 Introduction Lynch syndrome (LS;[MIM] 120435), is an autosomal domi- nant disease with early onset of colorectal cancer (CRC) and other extracolonic cancers including endometrium-, stomach-, small intestine-, hepatobiliary tract-, urinary Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10689-019-00130-y) contains supplementary material, which is available to authorized users. * Rihab Ben Sghaier Rihab28biologiste@gmail.com 1 Cytogenetic, Molecular Genetics and Human Reproduction Biology – Farhat, HACHED Hospital, Sousse, Tunisia 2 Pathology Department, Leiden University Medical Centre (LUMC), Leiden, The Netherlands 3 Cytology and Anatomopathology Department, Farhat HACHED Hospital, Sousse, Tunisia 4 Gastroenterology Department, Sahloul Hospital, Sousse, Tunisia 5 Present Address: Sousse, Tunisia 6 Carcinology Department, Farhat HACHED Hospital, Sousse, Tunisia 7 Gastroenterology Department, Mohamed Taahar Maamouri Hospital, Nabeul, Tunisia 8 Gastroenterology Department, Fatouma Bourguiba Hospital, Monastir, Tunisia 9 General Surgery Department, Farhat HACHED Hospital, Sousse, Tunisia