Journal Article

DKFZ-2019-02467

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways.

Srivastava, A. (First author)DKFZ* ; Kumar, A.DKFZ* ; Giangiobbe, S.DKFZ* ; Bonora, E. ; Hemminki, K.DKFZ* ; Försti, A.DKFZ* ; Bandapalli, O. R. (Last author)DKFZ*

2019
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/biom9100605

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.

Note: 2019, 9(10), 605

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Contributing Institute(s):

1. Molekular-Genetische Epidemiologie (C050)
2. B062 Pädiatrische Neuroonkologie (B062)
3. DKTK Heidelberg (L101)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2019

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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