Table 1.
Sources of genetic heterogeneity known to predict outcome/response to drugs currently administered to colorectal cancer patients.
| Genetic Source | Heterogeneity | Drug | Clinical Significance | Sample Source | Analysis | References |
|---|---|---|---|---|---|---|
| RAS (KRAS, NRAS) | Mutations | Anti-EGFR antibodies | Predictive | Primary and metastatic tissue, CTC, cfDNA | Next-generation and Sanger sequencing, BEAMing®, high-performance liquid chromatography, dropled dPCR, qPCR | [61,62,63,78,79,89,95,96,97,98,99] |
| BRAF | Mutations | Chemotherapy and targeted agents | Prognostic, possible predictive (anti-EGFR antibodies) | Primary and metastatic tissue, cfDNA | Next-generation and Sanger sequencing, high-performance liquid chromatography, BEAMing®, qPCR | [62,78,89,96,97,100,101,102,103] |
| MMR system (e.g., MLH1 gene) | Mutations (hereditary CRC) or CpG island methylation (sporadic CRC) | Chemotherapy in adjuvant setting | Prognostic, possible predictive to adjuvant 5-FU-based regimens | Primary tissue | IHC, (q)PCR | [9,103,104,105,106,107,108,109,110,111] |
| PI3K | Mutations | Anti-EGFR antibodies | Possible predictive | Primary and metastatic tissue, cfDNA | Next-generation and Sanger sequencing, BEAMing®, qPCR | [78,96,112] |
| cMET | Expression | Anti-EGFR antibodies | Possible prognostic and predictive | Primary and metastatic tissue | Expression microarrays, IHC | [43,113,114] |
| EGFR | Mutations, amplifications | Anti-EGFR antibodies | Possible predictive | Primary and metastatic tissue, cfDNA | Next-generation and Sanger sequencing, BEAMing®, qPCR, FISH | [62,92,115] |