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Identification of a novel GREM1 duplication in a patient with multiple colon polyps

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Abstract

Hereditary mixed polyposis syndrome (HMPS) is a hereditary syndrome that is characterized by multiple colon polyps of mixed pathologic subtypes and an increased risk for colorectal cancer. A 40 kb duplication in the 5′ regulatory region of the GREM1 gene was recently found to be the causal mutation in a subset of Ashkenazi Jewish families with HMPS. Given this discovery, the GREM1 5′ regulatory region is now analyzed on many different multi-gene cancer panels, however the data on duplications distinct from the 40 kb duplication remains minimal. Herein we report a novel 24 kb tandem duplication of the 5′ regulatory region of GREM1 in a patient without Ashkenazi Jewish heritage, who had a family history that was concerning for Lynch syndrome and satisfied Amsterdam II criteria. This is only the third reported GREM1 duplication separate from the 40 kb Ashkenazi Jewish duplication, and is the only reported duplication to selectively involve exon 1 of GREM1. This finding supports comprehensive testing of the GREM1 regulatory region in families of all ethnicities with multiple colon polyps or colon cancer, and when Lynch syndrome is suspected.

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Funding

The Lustgarten Family Colon Cancer Research Fund (AR) and NIH/NIDDK Grant 1K08DK106489 (BK).

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Danielle B. McKenna & Payal D. Shah

  2. Color Genomics, Burlingame, CA, 94010, USA

    Jeroen Van Den Akker, Alicia Y. Zhou, Lauren Ryan, Annette Leon & Robert O’Connor

  3. Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Anil K. Rustgi & Bryson W. Katona

Authors
  1. Danielle B. McKenna
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  2. Jeroen Van Den Akker
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  3. Alicia Y. Zhou
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  4. Lauren Ryan
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  5. Annette Leon
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  6. Robert O’Connor
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  7. Payal D. Shah
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  8. Anil K. Rustgi
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  9. Bryson W. Katona
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Corresponding author

Correspondence to Bryson W. Katona.

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McKenna, D.B., Van Den Akker, J., Zhou, A.Y. et al. Identification of a novel GREM1 duplication in a patient with multiple colon polyps. Familial Cancer 18, 63–66 (2019). https://doi.org/10.1007/s10689-018-0090-6

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  • DOI: https://doi.org/10.1007/s10689-018-0090-6

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