TY  - JOUR
AU  - Srivastava, Aayushi
AU  - Miao, Beiping
AU  - Skopelitou, Diamanto
AU  - Kumar, Varun
AU  - Kumar, Abhishek
AU  - Paramasivam, Nagarajan
AU  - Bonora, Elena
AU  - Hemminki, Kari
AU  - Försti, Asta
AU  - Bandapalli, Obul Reddy
TI  - A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer.
JO  - Cancers
VL  - 12
IS  - 6
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2020-01245
SP  - 1441
PY  - 2020
N1  - #EA:B062#EA:C050#LA:B062#LA:C050#
AB  - Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we report in silico analyses and in vitro experiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of the Protection of Telomeres 1 (POT1) gene in one of the families. The results showed a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293T cells carrying POT1 p.V29L showed increased telomere length in comparison to wild-type cells, suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. While one germline mutation in POT1 has already been reported in a melanoma-prone family with prevalence of thyroid cancers, we report the first of such mutations in a family affected solely by NMTCs, thus expanding current knowledge on shelterin complex-associated cancers.
LB  - PUB:(DE-HGF)16
C6  - pmid:32492864
DO  - DOI:10.3390/cancers12061441
UR  - https://inrepo02.dkfz.de/record/156940
ER  -