| Added by | mollevi |
|---|---|
| Last modified by | ircm doc |
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Circulating DNA Demonstrates Convergent Evolution and Common Resistance Mechanisms during Treatment of Colorectal Cancer |
| Creator | Thierry et al. |
| Author | Alain R. Thierry |
| Author | Brice Pastor |
| Author | Zhi-Qin Jiang |
| Author | Anastasia D. Katsiampoura |
| Author | Christine Parseghian |
| Author | Jonathan M. Loree |
| Author | Michael J. Overman |
| Author | Cynthia Sanchez |
| Author | Safia El Messaoudi |
| Author | Marc Ychou |
| Author | Scott Kopetz |
| Abstract | Purpose: Liquid biopsies allow the tracking of clonal dynamics and detection of mutations during treatment.Experimental Design: We evaluated under blinded conditions the ability of cell-free DNA (cfDNA) to detect RAS/BRAF mutations in the plasma of 42 metastatic colorectal cancer patients treated on a phase Ib/II trial of FOLFOX and dasatinib, with or without cetuximab.Results: Prior to treatment, sequencing of archival tissue detected mutations in 25 of 42 patients (60%), while the cfDNA assay detected mutations in 37 of 42 patients (88%). Our cfDNA assay detected mutations with allele frequencies as low as 0.01%. After exposure to treatment, 41 of 42 patients (98%) had a cfDNA-detected RAS/BRAF mutation. Of 21 patients followed with serial measurements who were RAS/BRAF mutant at baseline, 11 (52%) showed additional point mutation following treatment and 3 (14%) no longer had detectable levels of another mutant allele. Of RAS/BRAF wild-type tumors at baseline, 4 of 5 (80%) showed additional point mutations. cfDNA quantitative measurements from this study closely mirrored changes in CEA and CT scan results, highlighting the importance of obtaining quantitative data beyond the mere presence of a mutation.Conclusions: Our findings demonstrate the development of new RAS/BRAF mutations in patients regardless of whether they had preexisting mutations in the pathway, demonstrating a convergent evolutionary pattern. Clin Cancer Res; 23(16); 4578-91. ©2017 AACR. |
| Publication | Clinical Cancer Research: An Official Journal of the American Association for Cancer Research |
| Volume | 23 |
| Issue | 16 |
| Pages | 4578-4591 |
| Date | Aug 15, 2017 |
| Journal Abbr | Clin. Cancer Res. |
| Language | eng |
| DOI | 10.1158/1078-0432.CCR-17-0232 |
| ISSN | 1078-0432 |
| Library Catalog | PubMed |
| Extra | PMID: 28400427 PMCID: PMC5562356 |
| Tags | Antineoplastic Combined Chemotherapy Protocols, Cell-Free Nucleic Acids, Cetuximab, Clonal Evolution, Colorectal Neoplasms, Dasatinib, Drug Resistance, Neoplasm, Fluorouracil, Gene Frequency, Humans, Leucovorin, Mutation, Organoplatinum Compounds, original, Outcome Assessment (Health Care), Proto-Oncogene Proteins B-raf, ras Proteins |
| Date Added | 2018/11/13 - 17:25:54 |
| Date Modified | 2025/01/09 - 15:24:11 |
Institut de Recherche en Cancérologie de
