Aims In metastatic colorectal carcinomas (mCRC), RAS/RAF genes mutations are first tested to determine the eligibility for anti-EGFR (Epidermal Growth Factor Receptor) therapy in combination with conventional cytotoxic agents. Recent advancements in next-generation sequencing (NGS) have highlighted the potential of multi-gene panels. This multi-gene analysis may provide useful information for the molecular characterisation of mCRC, other than the status of RAS/RAF genes. Aim of this study was to evaluate the feasibility of two NGS custom multi-gene panels in the characterisation of CRC cases and evaluating the relevance of PIK3CA mutation in a routine cohort of consecutive CRC cases.
Methods A total of 961 formalin-fixed and paraffin-embedded specimens from two medical centres (Bologna and Naples) were analysed using two lab-developed NGS multi-gene panels.
Results KRAS mutations (56.2%) were the more frequent alterations observed in our cohort. Intriguingly, PIK3CA mutations were more frequent (16.8%) than variants observed in the other two genes nowadays analysed in CRC clinical practice (NRAS and BRAF, 4.2% and 9.6%, respectively). Moreover, in more than 10% of samples, coexistent mutations were detected in our cohort of CRC.
Conclusions Our study demonstrates the feasibility and efficacy of lab-developed targeted multi-gene NGS panels in the clinical practice of CRC. Moreover, the data lead to hypothesise that PIK3CA mutations, together with those of RAS/BRAF, worth to be further investigated in clinical CRC specimens.
- colorectal cancer
- diagnostic techniques and procedures
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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GT and GT are joint senior authors.
Handling editor Runjan Chetty.
Twitter @UmbertoMalapel1, @PasqualePisapia
DdB and UM contributed equally.
Contributors Conceptualisation, DdB and UM; methodology, DdB, UM, MV, PP, GA, FP, ADL, TM, GR, AI; formal analysis, DdB, UM, PP, FP; data curation, PP, GA, FP, ADL, GR, TM, AP; writing—original draft preparation, DdB, UM; supervision, AP, GTallini, GTroncone; project administration, GTallini, GTroncone; funding acquisition, GTallini, GTroncone. All authors have read and agreed to the published version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests UM reports personal fees (as a speaker or advisor) from Boehringer Ingelheim, ThermoFisher Scientific, AstraZeneca, Roche, MSD (Merck Sharp & Dohme), Amgen and Merck, Diaceutics and Eli Lilly, which are unrelated to the current work.
Provenance and peer review Not commissioned; externally peer reviewed.
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