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Table 2 Association of genome instability, alterations and immune therapy response

From: Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response

Source of genome instability Mutational profile/burden Neoantigen load Response to immunotherapy References
POLE mutation (germline or somatic) Single nucleotide variants (SNVs)/ultra-hypermutated High load Checkpoint blockade responsive [58, 59]
BRCA1/2 mutation (germline) Frameshift indels/elevated proportion vs SNVs Medium load/elevated number of strong binders Checkpoint blockade responsive [60]
Lynch syndrome (MSH1, MLH2, MLH6, PMS2) SNVs and indels/hypermutated High load/elevated number of strong binders Checkpoint blockade responsive, personalized vaccine responsive [57, 61]
VHL, SETD2, BAP1, KDM5C, FHIT defects Frameshift indels/elevated proportion vs SNVs Medium load/elevated number of strong binders Checkpoint blockade responsive [40, 62, 63]
Xeroderma pigmentosum defect (DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, or XPC) SNVs/ultra-hypermutated High load Checkpoint blockade responsive [64]
Constitutional mismatch repair deficiency syndrome (CMMRD): biallelic germline mutations in Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2) SNVs/hypermutated High load Checkpoint blockade responsive [65, 66]