Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal Carcinoma: The Way Forward for Personalized Treatment? A Single-Center Experience

Int J Mol Sci. 2024 Oct 15;25(20):11071. doi: 10.3390/ijms252011071.

Abstract

The efficacy and cost-effectiveness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remain uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), and BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in five patients (2.8%) and SMO in four patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in three patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on number of mutations. In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.

Keywords: druggable targets; metastatic colorectal cancer; molecular biomarkers; multigene panel; next-generation sequencing.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Female
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Precision Medicine* / methods
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human

Grants and funding

This work was partly supported thanks to the contribution of Ricerca Corrente by the Italian Ministry of Health within the research line “Precision, gender and ethnicity-based medicine and geroscience: genetic-molecular mechanisms in the development, characterization and treatment of tumors”.