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A new POT1 germline mutation—expanding the spectrum of POT1-associated cancers

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Abstract

Melanomas are associated with several hereditary conditions. We present a large family with several family members affected with primary melanomas and dysplastic nevi as well as thyroid cancer and other malignant tumors. Clinical work-up did not reveal a mutation in any of the genes usually considered with evaluation for predisposition to melanoma (BRCA1/2, CDKN2A, CDK4, PTEN, TP53). Whole exome sequencing of five affected family members showed a new variant in POT1. POT1 is associated with the telomere shelterin complex that regulates telomere protection and telomerase access. Germline mutations in POT1 were recently shown to be associated with hereditary predisposition to melanoma. Our findings support a role of POT1 germline mutations in cancer predisposition beyond melanoma development, suggesting a broader phenotype of the POT1-associated tumor predisposition syndrome that might also include thyroid cancer as well as possibly other malignant tumors.

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Acknowledgements

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA046592. TE is sponsored by the American Heart Association (14SDG17990000) and the NIH (1R01HL130106-01). We thank the University of Michigan DNA Sequencing Core for performing sequencing analysis. We are thankful to our patients in our registries allowing us to work with them clinically and in research.

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    Authors and Affiliations

    1. Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, 48109, USA

      Tremika Le-Shan Wilson, Namita Hattangady, Antonio Marcondes Lerario & Tobias Else

    2. Division of Cancer Genetics, Northwestern Medicine, Chicago, IL, 60611, USA

      Carmen Williams

    3. Department of Internal Medicine, Division of Molecular Medicine, University of Michigan, Ann Arbor, MI, 48109, USA

      Erika Koeppe, Shane Quinonez & Jenae Osborne

    4. Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA

      Kelly B. Cha

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    1. Tremika Le-Shan Wilson
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    Correspondence to Tobias Else.

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    Tremika Le-Shan Wilson, Namita Hattangady and Antonio Marcondes Lerario have contributed equally to this work.

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    Wilson, T.LS., Hattangady, N., Lerario, A.M. et al. A new POT1 germline mutation—expanding the spectrum of POT1-associated cancers. Familial Cancer 16, 561–566 (2017). https://doi.org/10.1007/s10689-017-9984-y

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