In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 12 ( 2018-12), p. 6068-6076
Abstract:
Two familial forms of colorectal cancer ( CRC ), Lynch syndrome ( LS ) and familial adenomatous polyposis ( FAP ), are caused by rare mutations in DNA mismatch repair genes ( MLH 1 , MSH 2 , MSH 6 , PMS 2 ) and the genes APC and MUTYH , respectively. No information is available on the presence of high‐risk CRC mutations in the Romanian population. We performed whole‐genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical ( IHC ) staining for MLH 1 , MSH 2 , MSH 6 , and PMS 2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH 1 , one in MSH 6 , one in PMS 2 , and three in APC . Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants ( MLH 1 :p.Lys84ThrfsTer4, MLH 1 :p.Ala586CysfsTer7, PMS 2 :p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic ( MLH 1 :c.1559‐1G 〉 C).
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
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