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dc.contributor.authorRaskin, L
dc.contributor.authorGuo, Y
dc.contributor.authorDu, L
dc.contributor.authorClendenning, M
dc.contributor.authorRosty, C
dc.contributor.authorLindor, NM
dc.contributor.authorGruber, SB
dc.contributor.authorBuchanan, DD
dc.date.accessioned2020-12-21T03:57:49Z
dc.date.available2020-12-21T03:57:49Z
dc.date.issued2017-11-07
dc.identifierpii: 18596
dc.identifier.citationRaskin, L., Guo, Y., Du, L., Clendenning, M., Rosty, C., Lindor, N. M., Gruber, S. B. & Buchanan, D. D. (2017). Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort. ONCOTARGET, 8 (55), pp.93450-93463. https://doi.org/10.18632/oncotarget.18596.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/257429
dc.description.abstractThe underlying genetic cause of colorectal cancer (CRC) can be identified for 5-10% of all cases, while at least 20% of CRC cases are thought to be due to inherited genetic factors. Screening for highly penetrant mutations in genes associated with Mendelian cancer syndromes using next-generation sequencing (NGS) can be prohibitively expensive for studies requiring large samples sizes. The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA pooling NGS strategy. We identified 264 variants in 38 genes that were observed only in cases, comprising either very rare (minor allele frequency <0.001) or not previously reported (n=90, 34%) in reference databases, including six stop-gain, three frameshift, and 255 non-synonymous variants predicted to be damaging. We found novel germline mutations in established CRC genes MLH1, APC, and POLE, and likely pathogenic variants in cancer susceptibility genes BAP1, CDH1, CHEK2, ENG, and MSH3. For the candidate CRC genes, we identified likely pathogenic variants in the helicase domain of POLQ and in the LRIG1, SH2B3, and NOS1 genes and present their clinicopathological characteristics. Using a DNA pooling NGS strategy, we identified novel germline mutations in established CRC susceptibility genes in familial CRC cases. Further studies are required to support the role of POLQ, LRIG1, SH2B3 and NOS1 as CRC susceptibility genes.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTargeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.18596
melbourne.affiliation.departmentClinical Pathology
melbourne.source.titleOncotarget
melbourne.source.volume8
melbourne.source.issue55
melbourne.source.pages93450-93463
dc.rights.licenseCC BY
melbourne.elementsid1273137
melbourne.contributor.authorClendenning, Mark
melbourne.contributor.authorBuchanan, Daniel
dc.identifier.eissn1949-2553
melbourne.identifier.fundernameidNATIONAL INSTITUTE OF HEALTH, 5U24CA097735 - 07
melbourne.identifier.fundernameidNATIONAL INSTITUTE OF HEALTH, 2U01CA167551-07
melbourne.accessrightsOpen Access


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