Development, technical validation, and clinical application of a multigene panel for hereditary gastrointestinal cancer and polyposis

Maria Teresa Ricci, Sara Volorio, Stefano Signoroni, Paolo Mariani, Frederique Mariette, Domenico Sardella, Valeria Pensotti, Marco Vitellaro

Research output: Contribution to journalArticlepeer-review


Introduction: Recent advances in technology and research are rapidly changing the diagnostic approach to hereditary gastrointestinal cancer (HGIC) syndromes. Although the practice of clinical genetics is currently transitioning from targeted criteria-based testing to multigene panels, important challenges remain to be addressed. The aim of this study was to develop and technically validate the performance of a multigene panel for HGIC. Methods: CGT-colon-G14 is an amplicon-based panel designed to detect single nucleotide variants and small insertions/deletions in 14 well-established or presumed high-penetrance genes involved in HGIC. The assay parameters tested were sensitivity, specificity, accuracy, and inter-run and intra-run reproducibility. Performance and clinical impact were determined using 48 samples of patients with suspected HGIC/polyposis previously tested with the targeted approach. Results: The CGT-colon-G14 panel showed 99.99% accuracy and 100% inter- and intra-run reproducibility. Moreover, panel testing detected 1 actionable pathogenic variant and 16 variants with uncertain clinical impact that were missed by the conventional approach because they were located in genes not previously analyzed. Conclusion: Introduction of the CGT-colon-G14 panel into the clinic could provide a higher diagnostic yield than a step-wise approach; however, results may not always be straightforward without the implementation of new genetic counseling models.

Original languageEnglish
Pages (from-to)338-352
Number of pages15
Issue number4
Publication statusPublished - Aug 1 2019


  • genetic counseling
  • Hereditary colorectal cancer
  • multigene testing
  • next-generation sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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