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EnglishThe 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.
Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients / Nicolazzo, Chiara; Barault, Ludovic; Caponnetto, Salvatore; Macagno, Marco; De Renzi, Gianluigi; Gradilone, Angela; Belardinilli, Francesca; Cortesi, Enrico; Di Nicolantonio, Federica; Gazzaniga, Paola. - In: CANCERS. - ISSN 2072-6694. - (2020), pp. 1-8.
| Titolo: | Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients | |
| Autori: | ||
| Data di pubblicazione: | 2020 | |
| Rivista: | ||
| Citazione: | Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients / Nicolazzo, Chiara; Barault, Ludovic; Caponnetto, Salvatore; Macagno, Marco; De Renzi, Gianluigi; Gradilone, Angela; Belardinilli, Francesca; Cortesi, Enrico; Di Nicolantonio, Federica; Gazzaniga, Paola. - In: CANCERS. - ISSN 2072-6694. - (2020), pp. 1-8. | |
| Handle: | http://hdl.handle.net/11573/1464090 | |
| Appartiene alla tipologia: | 01a Articolo in rivista |
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| File | Note | Tipologia | Licenza | |
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| NIcolazzo_Circulating_2020.pdf | Versione editoriale (versione pubblicata con il layout dell'editore) |  | Open Access Visualizza/Apri |
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