A Genomic Analysis Workflow for Colorectal Cancer Precision Oncology.
Clin Colorectal Cancer
; 18(2): 91-101.e3, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30981604
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Biomarcadores Tumorais
/
Genômica
/
Medicina de Precisão
/
Recidiva Local de Neoplasia
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Clin Colorectal Cancer
Assunto da revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália