Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
(2018) In Scientific Reports 8(1).- 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... (More)
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.
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- author
- Kumar, Abhishek ; Bandapalli, Obul Reddy ; Paramasivam, Nagarajan ; Giangiobbe, Sara ; Diquigiovanni, Chiara ; Bonora, Elena ; Eils, Roland ; Schlesner, Matthias ; Hemminki, Kari LU and Försti, Asta LU
- organization
- publishing date
- 2018-08-02
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 8
- issue
- 1
- article number
- 11635
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:30072699
- scopus:85051083154
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-018-29952-z
- language
- English
- LU publication?
- yes
- id
- 81a693c9-13fb-4300-b99b-5fe1cfc69ecb
- date added to LUP
- 2018-08-14 13:25:09
- date last changed
- 2024-06-10 15:59:14
@article{81a693c9-13fb-4300-b99b-5fe1cfc69ecb, abstract = {{<p>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.</p>}}, author = {{Kumar, Abhishek and Bandapalli, Obul Reddy and Paramasivam, Nagarajan and Giangiobbe, Sara and Diquigiovanni, Chiara and Bonora, Elena and Eils, Roland and Schlesner, Matthias and Hemminki, Kari and Försti, Asta}}, issn = {{2045-2322}}, language = {{eng}}, month = {{08}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family}}, url = {{http://dx.doi.org/10.1038/s41598-018-29952-z}}, doi = {{10.1038/s41598-018-29952-z}}, volume = {{8}}, year = {{2018}}, }