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@ARTICLE{Srivastava:156940,
author = {A. Srivastava$^*$ and B. Miao$^*$ and D. Skopelitou$^*$ and
V. Kumar and A. Kumar$^*$ and N. Paramasivam and E. Bonora
and K. Hemminki$^*$ and A. Försti$^*$ and O. R.
Bandapalli$^*$},
title = {{A} {G}ermline {M}utation in the {POT}1 {G}ene {I}s a
{C}andidate for {F}amilial {N}on-{M}edullary {T}hyroid
{C}ancer.},
journal = {Cancers},
volume = {12},
number = {6},
issn = {2072-6694},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2020-01245},
pages = {1441},
year = {2020},
note = {#EA:B062#EA:C050#LA:B062#LA:C050#},
abstract = {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.},
cin = {B062 / C050 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)C050-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32492864},
doi = {10.3390/cancers12061441},
url = {https://inrepo02.dkfz.de/record/156940},
}