{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:41:04Z","timestamp":1794109264976,"version":"4.8.0"},"reference-count":14,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,11]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS\/RAF pathway is the most frequently mutated, in \u223c50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed &amp;gt;10\u2009000 patients with different plasma cell disorders to describe the RAS\/RAF landscape. In this large cohort of patients, almost 61% of the patients presented a RAS\/RAF mutation at diagnosis or relapse, but much lower frequencies occurred in presymptomatic cases. Of note, the mutations were different from that observed in solid tumors (higher proportions of Q61 mutations). In 29 patients with 2 different mutations, we were able to perform single-cell sequencing, showing that in most cases, mutations occurred in different subclones, suggesting an ongoing mutational process. These findings suggest that the RAS\/RAF pathway is not an attractive target, both on therapeutic and residual disease assessment points of view.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023022295","type":"journal-article","created":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T14:59:10Z","timestamp":1713711550000},"page":"201-205","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["<i>RAS\/RAF<\/i>\n                    landscape in monoclonal plasma cell conditions"],"prefix":"10.1182","volume":"144","author":[{"given":"Anais","family":"Schavgoulidze","sequence":"first","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-6106","authenticated-orcid":false,"given":"Jill","family":"Corre","sequence":"additional","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Kemal","family":"Samur","sequence":"additional","affiliation":[{"name":"2Dana Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Mazzotti","sequence":"additional","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Pavageau","sequence":"additional","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-8689","authenticated-orcid":false,"given":"Aurore","family":"Perrot","sequence":"additional","affiliation":[{"name":"3Hematology Department, IUCT-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titouan","family":"Cazaubiel","sequence":"additional","affiliation":[{"name":"4Hematology Department, University Hospital, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Leleu","sequence":"additional","affiliation":[{"name":"5Hematology Department, University Hospital, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Macro","sequence":"additional","affiliation":[{"name":"6Hematology Department, University Hospital, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Belhadj","sequence":"additional","affiliation":[{"name":"7Hematology Department, University Hospital, Creteil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4045-9428","authenticated-orcid":false,"given":"Murielle","family":"Roussel","sequence":"additional","affiliation":[{"name":"8Hematology Department, University Hospital, Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Brechignac","sequence":"additional","affiliation":[{"name":"9Hematology Department, University Hospital, Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Montes","sequence":"additional","affiliation":[{"name":"10Hematology Department, University Hospital, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Caillot","sequence":"additional","affiliation":[{"name":"11Hematology Department, University Hospital, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6085-2163","authenticated-orcid":false,"given":"Laurent","family":"Frenzel","sequence":"additional","affiliation":[{"name":"12Hematology Department, University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Rey","sequence":"additional","affiliation":[{"name":"13Hematology Department, Centre Leon Berard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-4808","authenticated-orcid":false,"given":"Jean-Marc","family":"Schiano de Colella","sequence":"additional","affiliation":[{"name":"14Hematology Department, Institut Paoli Calmette, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Chalopin","sequence":"additional","affiliation":[{"name":"15Hematology Department, University Hospital, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Jacquet","sequence":"additional","affiliation":[{"name":"16Hematology Department, University Hospital, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Richez","sequence":"additional","affiliation":[{"name":"17Hematology Department, University Hospital, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Orsini-Piocelle","sequence":"additional","affiliation":[{"name":"18Hematology Department, General Hospital, Annecy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Fontan","sequence":"additional","affiliation":[{"name":"19Hematology Department, General Hospital, Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7653-711X","authenticated-orcid":false,"given":"Salomon","family":"Manier","sequence":"additional","affiliation":[{"name":"20Hematology Department, University Hospital, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-7724","authenticated-orcid":false,"given":"Ludovic","family":"Martinet","sequence":"additional","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sciambi","sequence":"additional","affiliation":[{"name":"21Mission Bio, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Mohty","sequence":"additional","affiliation":[{"name":"22Hematology Department, University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herve","family":"Avet-Loiseau","sequence":"additional","affiliation":[{"name":"1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"11","key":"2024071115205559500_bib1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"2024071115205559500_bib2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41375-018-0196-8","article-title":"A\u00a0high-risk, double-hit, group of newly diagnosed myeloma identified by genomic\u00a0analysis","volume":"33","author":"Walker","year":"2019","journal-title":"Leukemia"},{"issue":"9","key":"2024071115205559500_bib3","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/blood.2020008346","article-title":"Del17p without TP53 mutation confers poor prognosis in intensively treated newly diagnosed multiple myeloma patients","volume":"137","author":"Corre","year":"2021","journal-title":"Blood"},{"issue":"7339","key":"2024071115205559500_bib4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature09837","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nature"},{"key":"2024071115205559500_bib5","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1038\/ncomms3997","article-title":"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma","volume":"5","author":"Bolli","year":"2014","journal-title":"Nat Commun"},{"issue":"1","key":"2024071115205559500_bib6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ccr.2013.12.015","article-title":"Widespread genetic heterogeneity in\u00a0multiple myeloma: implications for targeted therapy","volume":"25","author":"Lohr","year":"2014","journal-title":"Cancer Cell"},{"issue":"27","key":"2024071115205559500_bib7","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1200\/JCO.20.00461","article-title":"Genome-wide somatic alterations in multiple myeloma reveal a superior outcome group","volume":"38","author":"Samur","year":"2020","journal-title":"J\u00a0Clin Oncol"},{"key":"2024071115205559500_bib8","doi-asserted-by":"crossref","first-page":"e467","DOI":"10.1038\/bcj.2016.72","article-title":"A\u00a0DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple\u00a0myeloma","volume":"6","author":"Bolli","year":"2016","journal-title":"Blood Cancer J"},{"key":"2024071115205559500_bib9","doi-asserted-by":"crossref","first-page":"11752","DOI":"10.18632\/oncotarget.2555","article-title":"BRAF vs RAS oncogenes: are mutations of the same pathway equal? differential signaling and therapeutic implications","volume":"23","author":"Oikonomou","year":"2014","journal-title":"Oncotarget"},{"key":"2024071115205559500_bib10","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1038\/s41467-022-31430-0","article-title":"The genetic\u00a0heterogeneity and drug resistance mechanisms of relapsed refractory multiple\u00a0myeloma","volume":"13","author":"Vo","year":"2022","journal-title":"Nat Commun"},{"issue":"12","key":"2024071115205559500_bib11","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1038\/s41375-018-0037-9","article-title":"Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups","volume":"32","author":"Bolli","year":"2018","journal-title":"Leukemia"},{"issue":"25","key":"2024071115205559500_bib12","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for lung cancers with KRAS p.G12C mutation","volume":"384","author":"Skoulidis","year":"2021","journal-title":"N\u00a0Engl J Med"},{"issue":"14","key":"2024071115205559500_bib13","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1182\/blood.2022017789","article-title":"A\u00a0phase 2 clinical trial of combined BRAF\/MEK inhibition for BRAFV600E-mutated multiple myeloma","volume":"141","author":"Giesen","year":"2023","journal-title":"Blood"},{"issue":"8","key":"2024071115205559500_bib14","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1038\/s41375-019-0469-x","article-title":"Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients","volume":"33","author":"Mithraprabhu","year":"2019","journal-title":"Leukemia"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/2\/201\/2234031\/blood_bld-2023-022295-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/2\/201\/2234031\/blood_bld-2023-022295-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:45:58Z","timestamp":1720698358000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/144\/2\/201\/515795\/RAS-RAF-landscape-in-monoclonal-plasma-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,7,11]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023022295","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}