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.
De Biase D., Malapelle U., De Leo A., Maloberti T., Visani M., Pisapia P., et al. (2021). Multi-gene custom panels for the characterisation of metastatic colorectal carcinoma in clinical practice: Express the role of PIK3CA mutations. JOURNAL OF CLINICAL PATHOLOGY, 0, 1-5 [10.1136/jclinpath-2021-207468].
Multi-gene custom panels for the characterisation of metastatic colorectal carcinoma in clinical practice: Express the role of PIK3CA mutations
De Biase D.;De Leo A.;Maloberti T.;Pession A.;Tallini G.;
2021
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
