Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family

Abstract Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleter...

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Autores principales:	Abhishek Kumar, Obul Reddy Bandapalli, Nagarajan Paramasivam, Sara Giangiobbe, Chiara Diquigiovanni, Elena Bonora, Roland Eils, Matthias Schlesner, Kari Hemminki, Asta Försti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c32193a2b57f403ea2c06d828e63cf5c
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spelling	oai:doaj.org-article:c32193a2b57f403ea2c06d828e63cf5c2021-12-02T11:40:17ZFamilial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family10.1038/s41598-018-29952-z2045-2322https://doaj.org/article/c32193a2b57f403ea2c06d828e63cf5c2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29952-zhttps://doaj.org/toc/2045-2322Abstract Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1 survived our pipeline. This variant is located in a highly conserved region across vertebrates in the peptidase_M14 domain (Pfam ID PF00246). The CPXM1 gene may be involved in adipogenesis and extracellular matrix remodelling and it has been suggested to be a tumour suppressor in breast cancer. However, the presence of the variant in the ExAC database suggests it to be a rare polymorphism or a low-penetrance risk allele. Overall, our pipeline is a comprehensive approach for prediction of predisposing variants for high-risk cancer families, for which a functional characterization is a crucial step to confirm their role in cancer predisposition.Abhishek KumarObul Reddy BandapalliNagarajan ParamasivamSara GiangiobbeChiara DiquigiovanniElena BonoraRoland EilsMatthias SchlesnerKari HemminkiAsta FörstiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abhishek Kumar Obul Reddy Bandapalli Nagarajan Paramasivam Sara Giangiobbe Chiara Diquigiovanni Elena Bonora Roland Eils Matthias Schlesner Kari Hemminki Asta Försti Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
description	Abstract Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1 survived our pipeline. This variant is located in a highly conserved region across vertebrates in the peptidase_M14 domain (Pfam ID PF00246). The CPXM1 gene may be involved in adipogenesis and extracellular matrix remodelling and it has been suggested to be a tumour suppressor in breast cancer. However, the presence of the variant in the ExAC database suggests it to be a rare polymorphism or a low-penetrance risk allele. Overall, our pipeline is a comprehensive approach for prediction of predisposing variants for high-risk cancer families, for which a functional characterization is a crucial step to confirm their role in cancer predisposition.
format	article
author	Abhishek Kumar Obul Reddy Bandapalli Nagarajan Paramasivam Sara Giangiobbe Chiara Diquigiovanni Elena Bonora Roland Eils Matthias Schlesner Kari Hemminki Asta Försti
author_facet	Abhishek Kumar Obul Reddy Bandapalli Nagarajan Paramasivam Sara Giangiobbe Chiara Diquigiovanni Elena Bonora Roland Eils Matthias Schlesner Kari Hemminki Asta Försti
author_sort	Abhishek Kumar
title	Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
title_short	Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
title_full	Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
title_fullStr	Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
title_full_unstemmed	Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
title_sort	familial cancer variant prioritization pipeline version 2 (fcvppv2) applied to a papillary thyroid cancer family
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c32193a2b57f403ea2c06d828e63cf5c
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Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family

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