| Title: |
Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients |
| Authors: |
Nicolazzo C.; Barault L.; Caponnetto S.; Macagno M.; De Renzi G.; Gradilone A.; Belardinilli F.; Cortesi E.; Di Nicolantonio F.; Gazzaniga P. |
| Contributors: |
Nicolazzo C.; Barault L.; Caponnetto S.; Macagno M.; De Renzi G.; Gradilone A.; Belardinilli F.; Cortesi E.; Di Nicolantonio F.; Gazzaniga P. |
| Publication Year: |
2020 |
| Collection: |
Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| Subject Terms: |
Circulating methylated DNA; Circulating tumor DNA; EGFR inhibitor; Liquid biopsy; Metastatic colorectal cancer; RAS mutation clearance |
| Description: |
The clearance of RAS mutations in plasma circulating tumor DNA (ctDNA) from originally RAS-mutant metastatic colorectal cancer (mCRC) has been recently demonstrated. Clinical trials investigating whether RAS mutant mCRC who “convert” to wild-type in plasma might benefit from EGFR blockade are ongoing. Detection of tumor-specific DNA methylation alterations in ctDNA has been suggested as a specific tool to confirm the tumoral origin of cell-free DNA. We monitored RAS clearance in plasma from patients with RAS-mutant mCRC at baseline (pre-treatment) (T0); after 4 months of first-line therapy (T1); at the time of first (T2) and second (T3) progression. A five-gene methylation panel was used to confirm the presence of ctDNA in samples in which RAS mutation clearance was detected. At T1, ctDNA analysis revealed wild-type RAS status in 83% of samples, all not methylated, suggesting at this time point the lack of ctDNA shedding. At T2, ctDNA analysis revealed wild-type RAS status in 83% of samples, of which 62.5% were found methylated. At T3, 50% of wild-type RAS samples were found methylated. Non-methylated samples were found in patients with lung or brain metastases. This five-gene methylation test might be useful to confirm the presence of ctDNA in RAS wild-type plasma samples. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/33291569; info:eu-repo/semantics/altIdentifier/wos/WOS:000601802100001; volume:12; issue:12; firstpage:1; lastpage:8; numberofpages:8; journal:CANCERS; http://hdl.handle.net/2318/1766201; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85097232780; https://www.mdpi.com/2072-6694/12/12/3633/htm |
| DOI: |
10.3390/cancers12123633 |
| Availability: |
http://hdl.handle.net/2318/1766201; https://doi.org/10.3390/cancers12123633; https://www.mdpi.com/2072-6694/12/12/3633/htm |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.4B0B02AE |
| Database: |
BASE |