Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer.
Colorectal Neoplasms, Hereditary Nonpolyposis
/ genetics
DNA Copy Number Variations
DNA Mismatch Repair
DNA, Neoplasm
/ blood
Endometrial Neoplasms
/ genetics
Exons
Female
High-Throughput Nucleotide Sequencing
Humans
Introns
Mismatch Repair Endonuclease PMS2
/ genetics
MutL Protein Homolog 1
/ genetics
MutS Homolog 2 Protein
/ genetics
Risk Factors
Untranslated Regions
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
12
2019
accepted:
19
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
17
9
2020
Statut:
epublish
Résumé
Germline variants inactivating the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.
Identifiants
pubmed: 32634176
doi: 10.1371/journal.pone.0235613
pii: PONE-D-19-36046
pmc: PMC7340288
doi:
Substances chimiques
DNA, Neoplasm
0
MLH1 protein, human
0
Untranslated Regions
0
PMS2 protein, human
EC 3.6.1.-
MSH2 protein, human
EC 3.6.1.3
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
MutL Protein Homolog 1
EC 3.6.1.3
MutS Homolog 2 Protein
EC 3.6.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0235613Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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