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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal
Laura Matteucci1, Francesco Giulio Sullo1, Chiara Gallio1
1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Via P. Maroncelli 40, 47014 Meldola, Italy.
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.
Insights
Multigene panel next-generation sequencing (NGS) identified actionable mutations in 40% of metastatic colorectal cancer patients, but only 1.1% received targeted therapy, indicating limited current clinical application for guiding treatment.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- The clinical utility of multigene panel next-generation sequencing (NGS) for guiding targeted therapies in metastatic colorectal cancer (mCRC) is not fully established.
- Assessing the prevalence of actionable mutations and their impact on treatment decisions is crucial for personalized medicine.
Purpose of the Study:
- To evaluate the efficacy of multigene panel NGS in identifying actionable molecular alterations in metastatic colorectal cancer (mCRC) patients.
- To determine the rate of genomically guided treatment and its association with patient outcomes.
Main Methods:
- Retrospective analysis of formalin-fixed paraffin-embedded tumor samples from 179 mCRC patients undergoing multigene panel NGS.
- Identification and characterization of mutations in key oncogenes and tumor suppressor genes.
- Correlation of mutation status with treatment received and survival data.
Main Results:
- No mutations were detected in 21.8% of patients; 46.4% had one mutation, and 31.8% had two or more.
- Common mutations included KRAS (48.6%), PIK3CA (22.4%), and BRAF (14.5%).
- Actionable molecular alterations were found in 40% of patients, but only 1.1% received genomically guided treatment, with no significant survival differences observed based on mutation number.
Conclusions:
- Multigene panel NGS can identify a substantial proportion of actionable mutations in mCRC patients, supporting personalized treatment strategies.
- Current application of NGS for guiding therapy in mCRC is limited due to low rates of genomically guided treatment and trial eligibility.
- Further research is needed to optimize the integration of NGS findings into routine clinical practice for mCRC management.
