Molecular Diagnostics of Colorectal Cancer Mutations

Colorectal cancer is driven by a spectrum of somatic alterations that inform prognosis, therapeutic selection and disease monitoring. Key driver mutations occur in KRAS, NRAS and BRAF genes, while amplifications of ERBB2 (HER2) and deficiency of mismatch-repair proteins manifest as microsatellite instability (MSI). Molecular diagnostics has evolved from single-gene assays towards multiplexed, high-throughput platforms. Real-time PCR-based tests and high-resolution melting analyses allow rapid hotspot screening, whereas next-generation sequencing (NGS) can characterise extended panels of oncogenes and tumour suppressors in formalin-fixed specimens. Liquid biopsy approaches, analysing circulating tumour DNA (ctDNA), offer minimally invasive detection of emerging resistance mutations. Mass spectrometry and microfluidics-based assays now deliver sensitive, reproducible mutation calls with low DNA input. The integration of these modalities into routine workflows underpins personalised treatment strategies, including anti-EGFR antibodies for RAS wild-type tumours, BRAF inhibitors, HER2-targeted agents and immune checkpoint blockade for MSI-high disease. As platforms continue to improve in speed, sensitivity and cost-effectiveness, molecular diagnostics is poised to enhance early detection, guide adaptive therapy and monitor minimal residual disease on a global scale.

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Molecular Diagnostics of Colorectal Cancer Mutations publication trend

The graph below shows the total number of articles in molecular diagnostics of colorectal cancer mutations across all publications each year (not limited to Nature Index journals).

Technical terms

KRAS mutation: A somatic alteration in the KRAS gene, often in codons 12 or 13, that predicts lack of response to anti-EGFR therapies.

Next-generation sequencing (NGS): High-throughput DNA sequencing technology that enables simultaneous analysis of multiple genes and mutation types.

Liquid biopsy: Non-invasive sampling of body fluids, most commonly plasma, to detect circulating tumour DNA (ctDNA) reflecting tumour mutations.

Microsatellite instability (MSI): A hypermutable phenotype due to deficient mismatch-repair proteins, associated with response to immunotherapy.

Peptide nucleic acid (PNA): A synthetic DNA analogue with high binding specificity used to block wild-type sequences in mutation detection assays.

Locked nucleic acid (LNA): A modified RNA nucleotide that increases probe affinity and specificity in molecular amplification techniques.

References

1. A novel platform for mutation detection in colorectal cancer using a PNA-LNA molecular switch. Biosensors and Bioelectronics (2024).
2. KRAS, NRAS, BRAF, HER2 and MSI Status in a Large Consecutive Series of Colorectal Carcinomas. International Journal of Molecular Sciences (2023).
3. Current and emerging biomarkers in metastatic colorectal cancer. Current Oncology (2019).
4. Detection of KRAS, NRAS and BRAF by mass spectrometry - a sensitive, reliable, fast and cost-effective technique. Diagnostic Pathology (2015).
5. Next Generation MUT-MAP, a High-Sensitivity High-Throughput Microfluidics Chip-Based Mutation Analysis Panel. PLOS ONE (2014).