title: A new POT1 germline mutation-expanding the spectrum of POT1-associated cancers.
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.
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Tremika Le-Shan
authors.initials: TL
authors.lastname: Wilson
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Namita
authors.initials: N
authors.lastname: Hattangady
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Antonio Marcondes
authors.initials: AM
authors.lastname: Lerario
authors.affiliation: Division of Cancer Genetics, Northwestern Medicine, Chicago, IL, 60611, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Koeppe
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Quinonez
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jenae
authors.initials: J
authors.lastname: Osborne
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, 48109, USA. telse@umich.edu.
authors.forename: Tobias
authors.initials: T
authors.lastname: Else
mesh_terms: D000328:Adult; D000368:Aged; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D010375:Pedigree; D000089804:Shelterin Complex; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D034501:Telomere-Binding Proteins / Q000235:genetics*; D000073359:Exome Sequencing
chemical_list: C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins
keywords: Melanoma; POT1; Telomere; Thyroid cancer