Publication
Title
Copy number load predicts outcome of metastatic colorectal cancer patients receiving bevacizumab combination therapy
Author
Abstract
Increased copy number alterations (CNAs) indicative of chromosomal instability (CIN) have been associated with poor cancer outcome. Here, we study CNAs as potential biomarkers of bevacizumab (BVZ) response in metastatic colorectal cancer (mCRC). We cluster 409 mCRCs in three subclusters characterized by different degrees of CIN. Tumors belonging to intermediate-to-high instability clusters have improved outcome following chemotherapy plus BVZ versus chemotherapy alone. In contrast, low instability tumors, which amongst others consist of POLE-mutated and microsatellite-instable tumors, derive no further benefit from BVZ. This is confirmed in 81 mCRC tumors from the phase 2 MoMa study involving BVZ. CNA clusters overlap with CRC consensus molecular subtypes (CMS); CMS2/4 xenografts correspond to intermediate-to-high instability clusters and respond to FOLFOX chemotherapy plus mouse avastin (B20), while CMS1/3 xenografts match with low instability clusters and fail to respond. Overall, we identify copy number load as a novel potential predictive biomarker of BVZ combination therapy.
Language
English
Source (journal)
Nature communications
Publication
2018
ISSN
2041-1723
Volume/pages
9 (2018) , 16 p.
Article Reference
4112
ISI
000446496100003
Pubmed ID
30291241
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
ANGIOPREDICT: Predictive Genomic Biomarkers Methods for Combination Bevacizumab (Avastin) Therapy in Metastatic Colorectal Cancer
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 09.11.2018
Last edited 20.09.2021
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