Familial cancer variant prioritization pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family

• Verfasst von: Kumar, Abhishek [VerfasserIn]
• Verfasst von: Bandapalli, Obul Reddy [VerfasserIn]
• Verfasst von: Paramasivam, Nagarajan [VerfasserIn]
• Verfasst von: Giangiobbe, Sara [VerfasserIn]
• Verfasst von: Diquigiovanni, Chiara [VerfasserIn]
• Verfasst von: Bonora, Elena [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Schlesner, Matthias [VerfasserIn]
• Verfasst von: Hemminki, Kari [VerfasserIn]
• Verfasst von: Försti, Asta [VerfasserIn]
• Titel: Familial cancer variant prioritization pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
• Verf.angabe: Abhishek Kumar, Obul Reddy Bandapalli, Nagarajan Paramasivam, Sara Giangiobbe, Chiara Diquigiovanni, Elena Bonora, Roland Eils, Matthias Schlesner, Kari Hemminki & Asta Försti
• E-Jahr: 2018
• Jahr: 02 August 2018
• Umfang: 12 S.
• Fussnoten: Gesehen am 14.11.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2018
• Band/Heft Quelle: 8(2018) Artikel-Nummer 11635, 12 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-018-29952-z
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1681856344

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.