Exome sequencing in a Swedish family with PMS2 mutation with varying penetrance of colorectal cancer: investigating the presence of genetic risk modifiers in colorectal cancer risk.
Journal
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
ISSN: 1473-5709
Titre abrégé: Eur J Cancer Prev
Pays: England
ID NLM: 9300837
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
pubmed:
23
9
2022
medline:
3
2
2023
entrez:
22
9
2022
Statut:
ppublish
Résumé
Lynch syndrome is caused by germline mutations in the mismatch repair (MMR) genes, such as the PMS2 gene, and is characterised by a familial accumulation of colorectal cancer. The penetrance of cancer in PMS2 carriers is still not fully elucidated as a colorectal cancer risk has been shown to vary between PMS2 carriers, suggesting the presence of risk modifiers. Whole exome sequencing was performed in a Swedish family carrying a PMS2 missense mutation [c.2113G>A, p.(Glu705Lys)]. Thirteen genetic sequence variants were further selected and analysed in a case-control study (724 cases and 711 controls). The most interesting variant was an 18 bp deletion in gene BAG1. BAG1 has been linked to colorectal tumour progression with poor prognosis and is thought to promote colorectal tumour cell survival through increased NF-κB activity. We conclude the genetic architecture behind the incomplete penetrance of PMS2 is complicated and must be assessed in a genome wide manner using large families and multifactorial analysis.
Identifiants
pubmed: 36134613
doi: 10.1097/CEJ.0000000000000769
pii: 00008469-202303000-00003
doi:
Substances chimiques
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
MutL Protein Homolog 1
EC 3.6.1.3
PMS2 protein, human
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113-118Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
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