Article Text
Abstract
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
- pathology
- molecular
- oncogenes
- DNA
- 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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Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Footnotes
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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