Molecular genetics of early-onset colorectal cancer

Table 1 Differences in early-onset colorectal cancer and later-onset colorectal cancer DNA mutations

Gene	Prevalence in EOCRC vs LOCRC1	Role in cancer
APC	Decreased[33,34,44,45]	Blocks β-catenin, tumor suppressor
CTNNB1	Increased[33,34]	β-catenin, potentiates Wnt signaling, proliferation, and stemness
RNF43	Increased[43]/NS[33]	E3 ligase, negative regulator of Wnt signaling
BRCA2	Increased[54]	Double stranded DNA repair, tumor suppressor
PHLPP1	Increased[54]	Promotes apoptosis, inhibits AKT
TOPORS	Increased[54]	Regulates TP53 stability, likely tumor suppressor
ATR	Increased[54]	PI3/PI4 kinase, activates checkpoint proteins
MYCBP2	Increased[54]	MYC binding protein, activates MYC
FBXW7	Increased[44,54]	Ubiquitin ligase component, ubiquitinates MYC
POLE	Increased[44,54]	DNA polymerase E subunit, proofreading and DNA repair
BRAF	Decreased[34,38,57]/increased[43]	Proto-oncogene, activates MAPK signaling
TP53	Decreased[38,52]	Cell cycle inhibitor, tumor suppressor
NOMO1	Increased[53,126]	Inhibits nodal signaling. Deletion increases CRC cell migration
MYC	Increased[50,51]/NS[43,47]	Proto-oncogenic transcription factor, promotes proliferation and stemness
DNMT3B	Decreased[43]	De-novo DNA methyltransferase
MET	Decreased[43]	Proto-oncogene, promotes cell growth and survival
PTEN	Increased[57]	Tumor suppressor, negatively regulates AKT signaling
KRAS	Decreased[99,120]	Proto-oncogene, activates oncogenic signaling pathways

¹Increase or decrease in the prevalence of genomic mutations or copy number variations in early-onset colorectal cancer compared with later-onset colorectal cancer tumors.

CRC: Colorectal cancer; NS: Not significant.