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Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel

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Abstract

We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type/normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

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Funding

The Israel Cancer Association funded the study.

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Author notes

    Authors and Affiliations

    1. Department of Gastroenterology, Soroka Medical Center, Beer-Sheva, Israel

      Naim Abu Freha & Alexander Fich

    2. Department of Gastroenterology, Beilinson Medical Center, Petah Tikva, Israel

      Yaara Leibovici Weissman, Orly Arbib Sneh, Alex Vilkin, Rachel Gingold, Yaron Niv & Zohar Levi

    3. The Raphael Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel

      Inbal Barnes Kedar & Yael Goldberg

    4. Department of Pathology, Hasharon Medical Center, Petah-Tikva, Israel

      Marisa Halpern

    5. Department of Pathology, Soroka Medical Center, Beer-Sheva, Israel

      Ignacio Sztarkier

    6. Genomics Research Center, Gene by Gene, Houston, TX, USA

      Doron M. Behar

    7. The Genetics Institute, Rambam Health Care Campus and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel

      Hagit N. Baris

    8. The Clalit Health Services, Personalized Genomic Service, Carmel, Haifa, Israel

      Flavio Lejbkowicz & Yaron Niv

    9. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

      Zohar Levi

    10. Early Detection and High Risk GI Cancer, Rabin Medical Center, Petah Tikva, Israel

      Zohar Levi

    Authors
    1. Naim Abu Freha
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    2. Yaara Leibovici Weissman
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    3. Alexander Fich
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    9. Alex Vilkin
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    10. Hagit N. Baris
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    13. Yaron Niv
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    14. Yael Goldberg
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    15. Zohar Levi
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    Corresponding author

    Correspondence to Zohar Levi.

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    There are no conflicts of interest for any of the authors.

    Additional information

    Yael Goldberg and Zohar Levi have contributed equally.

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    Cite this article

    Abu Freha, N., Leibovici Weissman, Y., Fich, A. et al. Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel. Familial Cancer 17, 79–86 (2018). https://doi.org/10.1007/s10689-017-0009-7

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    • DOI: https://doi.org/10.1007/s10689-017-0009-7

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