POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
02
07
2021
accepted:
23
07
2021
revised:
20
07
2021
pubmed:
8
8
2021
medline:
27
1
2022
entrez:
7
8
2021
Statut:
ppublish
Résumé
POLE, POLD1, and NTHL1 are involved in DNA replication and have recently been recognized as hereditary cancer-predisposing genes, because their alterations are associated with colorectal cancer and other tumors. POLE/POLD1-associated syndrome shows an autosomal dominant inheritance, whereas NTHL1-associated syndrome follows an autosomal recessive pattern. Although the prevalence of germline monoallelic POLE/POLD1 and biallelic NTHL1 pathogenic variants is low, they determine different phenotypes with a broad tumor spectrum overlapping that of other hereditary conditions like Lynch Syndrome or Familial Adenomatous Polyposis. Endometrial and breast cancers, and probably ovarian and brain tumors are also associated with POLE/POLD1 alterations, while breast cancer and other unusual tumors are correlated with NTHL1 pathogenic variants. POLE-mutated colorectal and endometrial cancers are associated with better prognosis and may show favorable responses to immunotherapy. Since POLE/POLD1-mutated tumors show a high tumor mutational burden producing an increase in neoantigens, the identification of POLE/POLD1 alterations could help select patients suitable for immunotherapy treatment. In this review, we will investigate the role of POLE, POLD1, and NTHL1 genetic variants in cancer predisposition, discussing the potential future therapeutic applications and assessing the utility of performing a routine genetic testing for these genes, in order to implement prevention and surveillance strategies in mutation carriers.
Identifiants
pubmed: 34363023
doi: 10.1038/s41388-021-01984-2
pii: 10.1038/s41388-021-01984-2
doi:
Substances chimiques
Poly-ADP-Ribose Binding Proteins
0
POLD1 protein, human
EC 2.7.7.-
DNA Polymerase II
EC 2.7.7.7
DNA Polymerase III
EC 2.7.7.7
POLE protein, human
EC 2.7.7.7
Deoxyribonuclease (Pyrimidine Dimer)
EC 3.1.25.1
NTHL1 protein, human
EC 3.1.25.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
5893-5901Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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