A Genomic Analysis Workflow for Colorectal Cancer Precision Oncology

Giorgio Corti, Alice Bartolini, Giovanni Crisafulli, Luca Novara, Giuseppe Rospo, Monica Montone, Carola Negrino, Benedetta Mussolin, Michela Buscarino, Claudio Isella, Ludovic Barault, Giulia Siravegna, Salvatore Siena, Silvia Marsoni, Federica Di Nicolantonio, Enzo Medico, Alberto Bardelli

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The diagnosis of colorectal cancer (CRC) is routinely accomplished through histopathologic examination. Prognostic information and treatment decisions are mainly determined by TNM classification, first defined in 1968. In the last decade, patient-specific CRC genomic landscapes were shown to provide important prognostic and predictive information. Therefore, there is a need for developing next generation sequencing (NGS) and bioinformatic workflows that can be routinely used for the assessment of prognostic and predictive biomarkers.

MATERIALS AND METHODS: To foster the application of genomics in the clinical management of CRCs, the IDEA workflow has been built to easily adapt to the availability of patient specimens and the clinical question that is being asked. Initially, IDEA deploys ad-hoc NGS assays to interrogate predefined genomic target sequences (from 600 kb to 30 Mb) with optimal detection sensitivity. Next, sequencing data are processed through an integrated bioinformatic pipeline to assess single nucleotide variants, insertions and deletions, gene copy-number alterations, and chromosomal rearrangements. The overall results are gathered into a user-friendly report.

RESULTS: We provide evidence that IDEA is capable of identifying clinically relevant molecular alterations. When optimized to analyze circulating tumor DNA, IDEA can be used to monitor response and relapse in the blood of patients with metastatic CRC receiving targeted agents. IDEA detected primary and secondary resistance mechanisms to ERBB2 blockade including sub-clonal RAS and BRAF mutations.

CONCLUSIONS: The IDEA workflow provides a flexible platform to integrate NGS and bioinformatic tools for refined diagnosis and management of patients with advanced CRC.

Original languageEnglish
Pages (from-to)91-101.e3
JournalClinical Colorectal Cancer
Issue number2
Publication statusPublished - Jun 2019


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