Non-exonuclease domain POLE mutations and their biological significance in colorectal cancer

doi:10.3748/wjg.118014

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Aug 28, 2026; 32(32): 118014
Published online Aug 28, 2026. doi: 10.3748/wjg.118014

Table 2 Co-mutational landscape of non-exonuclease domain mutations DNA polymerase epsilon-mutant colorectal cancer

Gene	Pathway/function	Role in CRC	*Interaction with POLE* non-EDM**
MLH3	Mismatch repair	DNA repair	Partial repair deficiency → synergistic mutagenesis
MSH3	Mismatch repair	Indel repair	MSI-L phenotype, replication error accumulation
KRAS	MAPK signaling	Oncogenic driver	Sustains proliferation in unstable genome
BRAF	MAPK signaling	Prognostic/driver	Less frequent, may define subgroups
PIK3CA	PI3K/AKT pathway	Growth and survival	Supports tumor progression alongside instability

CRC: Colorectal cancer; EDM: Exonuclease domain mutation; MAPK: Mitogen-activated protein kinase; MLH3: MutL homolog 3; MSH3: MutS homolog 3; MSI-L: Low levels of microsatellite instability; PIK3CA: Phosphoinositide 3-kinase catalytic subunit alpha; POLE: DNA polymerase epsilon.

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Citation: Kyrochristou I, Kyrochristou GD, Lianos GD. Non-exonuclease domain POLE mutations and their biological significance in colorectal cancer. World J Gastroenterol 2026; 32(32): 118014
URL: https://www.wjgnet.com/1007-9327/full/v32/i32/118014.htm
DOI: https://dx.doi.org/10.3748/wjg.118014

Kyrochristou I, Kyrochristou GD, Lianos GD. Non-exonuclease domain POLE mutations and their biological significance in colorectal cancer. World J Gastroenterol 2026; 32(32): 118014 [DOI: 10.3748/wjg.118014]

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