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

作者：Wilson Tremika Le Shan; Hattangady Namita; Lerario Antonio Marcondes; Williams Carmen; Koeppe Erika; Quinonez Shane; O**orne Jenae; Cha Kelly B; Else Tobias^*

来源：Familial Cancer, 2017, 16(4): 561-566.

DOI：10.1007/s10689-017-9984-y

• Melanoma
• Telomere
• POT1
• Thyroid cancer

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.

• 出版日期2017-10