Giorgio Corti1, Alice Bartolini1, Giovanni Crisafulli2, Luca Novara1, Giuseppe Rospo1, Monica Montone1, Carola Negrino1, Benedetta Mussolin1, Michela Buscarino1, Claudio Isella2, Ludovic Barault2, Giulia Siravegna2, Salvatore Siena3, Silvia Marsoni4, Federica Di Nicolantonio5, Enzo Medico6, Alberto Bardelli7. 1. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy. 2. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; University of Turin, Department of Oncology, Candiolo (TO), Italy. 3. Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; Department of Oncology and Haematology-Oncology, University of Milano, Milano, Italy. 4. Department of Oncology and Haematology-Oncology, University of Milano, Milano, Italy; FIRC Institute of Molecular Oncology (IFOM), Milan, Italy. 5. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; University of Turin, Department of Oncology, Candiolo (TO), Italy. Electronic address: federica.dinicolantonio@unito.it. 6. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; University of Turin, Department of Oncology, Candiolo (TO), Italy. Electronic address: enzo.medico@unito.it. 7. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; University of Turin, Department of Oncology, Candiolo (TO), Italy. Electronic address: alberto.bardelli@unito.it.
Abstract
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.
RCT Entities:
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.
Authors: Alberto Bardelli; Sabrina Arena; Erika Durinikova; Nicole M Reilly; Kristi Buzo; Elisa Mariella; Rosaria Chilà; Annalisa Lorenzato; João M L Dias; Gaia Grasso; Federica Pisati; Simona Lamba; Giorgio Corti; Andrea Degasperi; Carlotta Cancelliere; Gianluca Mauri; Pietro Andrei; Michael Linnebacher; Silvia Marsoni; Salvatore Siena; Andrea Sartore-Bianchi; Serena Nik-Zainal; Federica Di Nicolantonio Journal: Clin Cancer Res Date: 2022-09-01 Impact factor: 13.801
Authors: Alessandra Merlini; Maria Laura Centomo; Giulio Ferrero; Giulia Chiabotto; Umberto Miglio; Enrico Berrino; Giorgia Giordano; Silvia Brusco; Alberto Pisacane; Elena Maldi; Ivana Sarotto; Federica Capozzi; Cristina Lano; Claudio Isella; Giovanni Crisafulli; Massimo Aglietta; Angelo Paolo Dei Tos; Marta Sbaraglia; Dario Sangiolo; Lorenzo D'Ambrosio; Alberto Bardelli; Ymera Pignochino; Giovanni Grignani Journal: Front Oncol Date: 2022-08-30 Impact factor: 5.738