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@ARTICLE{Srivastava:147346,
author = {A. Srivastava$^*$ and A. Kumar$^*$ and S. Giangiobbe$^*$
and E. Bonora and K. Hemminki$^*$ and A. Försti$^*$ and O.
R. Bandapalli$^*$},
title = {{W}hole {G}enome {S}equencing of {F}amilial
{N}on-{M}edullary {T}hyroid {C}ancer {I}dentifies {G}ermline
{A}lterations in {MAPK}/{ERK} and {PI}3{K}/{AKT} {S}ignaling
{P}athways.},
journal = {Biomolecules},
volume = {9},
number = {10},
issn = {2218-273X},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2019-02467},
pages = {605},
year = {2019},
note = {2019, 9(10), 605},
abstract = {Evidence of familial inheritance in non-medullary thyroid
cancer (NMTC) has accumulated over the last few decades.
However, known variants account for a very small percentage
of the genetic burden. Here, we focused on the
identification of common pathways and networks enriched in
NMTC families to better understand its pathogenesis with the
final aim of identifying one novel high/moderate-penetrance
germline predisposition variant segregating with the disease
in each studied family. We performed whole genome sequencing
on 23 affected and 3 unaffected family members from five
NMTC-prone families and prioritized the identified variants
using our Familial Cancer Variant Prioritization Pipeline
(FCVPPv2). In total, 31 coding variants and 39 variants
located in upstream, downstream, 5' or 3' untranslated
regions passed FCVPPv2 filtering. Altogether, 210 genes
affected by variants that passed the first three steps of
the FCVPPv2 were analyzed using Ingenuity Pathway Analysis
software. These genes were enriched in tumorigenic signaling
pathways mediated by receptor tyrosine kinases and G-protein
coupled receptors, implicating a central role of PI3K/AKT
and MAPK/ERK signaling in familial NMTC. Our approach can
facilitate the identification and functional validation of
causal variants in each family as well as the screening and
genetic counseling of other individuals at risk of
developing NMTC.},
cin = {C050 / B062 / L101},
ddc = {570},
cid = {I:(DE-He78)C050-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31614935},
doi = {10.3390/biom9100605},
url = {https://inrepo02.dkfz.de/record/147346},
}