Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants

Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the alterations influence similar strength tumorigene...

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Bibliographic Details
Published in:Life science alliance 2024-01, Vol.7 (1), p.e202302290
Main Authors: Selves, Janick, de Castro E Gloria, Helena, Brunac, Anne-Cécile, Saffi, Jenifer, Guimbaud, Rosine, Brousset, Pierre, Hoffmann, Jean-Sébastien
Format: Article
Language:English
Subjects:
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Polymerase II - genetics
DNA Polymerase II - metabolism
DNA Replication
Endometrial Neoplasms - genetics
Endometrial Neoplasms - pathology
Female
Germ-Line Mutation
Humans
Mutation - genetics
Poly-ADP-Ribose Binding Proteins - genetics
Poly-ADP-Ribose Binding Proteins - metabolism
Review
Reviews
Tumor Microenvironment
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Summary:Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202302290