Genetic mutations associated with sensitivity to neoadjuvant chemotherapy in metastatic colon cancer: A case report and review of literature

Table 2 Summary of evidence for other gene mutations

Genes mutation	Ref.	Summary	Conclusion
CREBBP	Lin et al[37], 2020	TMB-high (> 11 mutations/Mb), male, mutation of RNF43, CREBBP, NOTCH3, PTCH1, CIC, DNMT1 and SPEN were all related to longer OS	CREBBP mutation may be related to higher immunogenicity such as TMB, high expression of mRNA related to immune response, highly infiltrating immune-active cells such as CD8+T cells, active immune-active pathways, and DNA damage repair pathways with an increased number of mutations
	Douglas et al[38],2020	When looking at the complete responder group, mutations were noted in endoscopic biopsy specimens from at least two patients in genes including ARID1A, JAK1, CREBBP, and MTOR (three patients each), that were not seen to be mutated in PR specimens	The authors identified multiple genetic variations in tumor DNA from rectal cancer patients who are poor responders to neoadjuvant chemoradiation, compared to complete responders
POLD1	Hühns et al[40], 2019	The authors performed POLE and POLD1 exonuclease domain Sanger sequencing of 271 unselected colorectal carcinomas and finally identified two microsatellite-stable tumors with somatic POLE p.P286R variants, both with ultrahigh TMBs as demonstrated by whole exome sequencing. In two tumors, a somatic POLE p.V411L and a POLD1 p.E279K, respectively, were found only focally, and TMBs were low. It is commonly assumed that compromise of one allele is sufficient, but this has not been specifically addressed	Taken together, including at least the more common DNA polymerase mutations in NGS panels allows for straightforward identification of hypermutator-type colorectal carcinomas which often may be "immunoreactive". This is important at least in young patients or when a metastasizing stage of disease has been reached and immune-checkpoint therapy enters deliberation
IKZF1	None	No eligible studies	No evidence
PRKCB	None	No eligible studies	No evidence

DNA: Deoxyribonucleic acid; mRNA: Messenger ribonucleic acid; NGS: Next generation sequencing; TMB: Tumor mutation burden.