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Article: Frequent functional activation of RAS signalling not explained by RAS/RAF mutations in relapsed/refractory multiple myeloma

TitleFrequent functional activation of RAS signalling not explained by RAS/RAF mutations in relapsed/refractory multiple myeloma
Authors
Issue Date2018
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2018, v. 8, article no. 13522 How to Cite?
AbstractRAS mutations are frequent in relapsed/refractory multiple myeloma (RRMM) but functional study in primary samples is scanty. Herein, in primary myeloma plasma cells of 17 suspected RRMM, functional activation of RAS signalling was studied by Western blot of phosphorylated ERK1/2 (phospho-ERK1/2). Moreover, activating mutations in KRAS, NRAS, BRAF, and ALK were studied by PCR and bidirectional direct sequencing. Furthermore, methylation of negative RAS signalling regulator genes, RASSF1A and RASD1, were analyzed by methylation-specific PCR. As evidenced by phospho-ERK1/2 over-expression, functional RAS activation was detected in 12 (75.0%) RRMM. Of patients with functional RAS activation, sequencing data showed only seven (58.3%) patients with one each had NRAS Q61H, NRAS Q61K, KRAS G12D, KRAS G12V, KRAS G13D, KRAS Q61P, or BRAF V600E mutation, whereas five (41.7%) patients had no RAS/RAF mutation. Conversely, patients without functional RAS activation had no RAS/RAF mutation. Moreover, none of the patients with functional RAS activation had ALK mutations, or methylation of RASSF1A and RASD1. Collectively, functional activation of RAS signalling was present in majority of RRMM but only about half (58.3%) accountable by RAS/RAF mutations. If verified in larger studies, clinical investigations of MEK inhibitors are warranted regardless of RAS/RAF mutations.
Persistent Identifierhttp://hdl.handle.net/10722/271990
ISSN
2017 Impact Factor: 4.122
2015 SCImago Journal Rankings: 2.073
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, KY-
dc.contributor.authorYao, Q-
dc.contributor.authorYuan, L-
dc.contributor.authorLi, Z-
dc.contributor.authorMa, ESK-
dc.contributor.authorChim, CS-
dc.date.accessioned2019-07-20T10:33:32Z-
dc.date.available2019-07-20T10:33:32Z-
dc.date.issued2018-
dc.identifier.citationScientific Reports, 2018, v. 8, article no. 13522-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/271990-
dc.description.abstractRAS mutations are frequent in relapsed/refractory multiple myeloma (RRMM) but functional study in primary samples is scanty. Herein, in primary myeloma plasma cells of 17 suspected RRMM, functional activation of RAS signalling was studied by Western blot of phosphorylated ERK1/2 (phospho-ERK1/2). Moreover, activating mutations in KRAS, NRAS, BRAF, and ALK were studied by PCR and bidirectional direct sequencing. Furthermore, methylation of negative RAS signalling regulator genes, RASSF1A and RASD1, were analyzed by methylation-specific PCR. As evidenced by phospho-ERK1/2 over-expression, functional RAS activation was detected in 12 (75.0%) RRMM. Of patients with functional RAS activation, sequencing data showed only seven (58.3%) patients with one each had NRAS Q61H, NRAS Q61K, KRAS G12D, KRAS G12V, KRAS G13D, KRAS Q61P, or BRAF V600E mutation, whereas five (41.7%) patients had no RAS/RAF mutation. Conversely, patients without functional RAS activation had no RAS/RAF mutation. Moreover, none of the patients with functional RAS activation had ALK mutations, or methylation of RASSF1A and RASD1. Collectively, functional activation of RAS signalling was present in majority of RRMM but only about half (58.3%) accountable by RAS/RAF mutations. If verified in larger studies, clinical investigations of MEK inhibitors are warranted regardless of RAS/RAF mutations.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleFrequent functional activation of RAS signalling not explained by RAS/RAF mutations in relapsed/refractory multiple myeloma-
dc.typeArticle-
dc.identifier.emailWong, KY: kwanumu@hku.hk-
dc.identifier.emailChim, CS: jcschim@hku.hk-
dc.identifier.authorityChim, CS=rp00408-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41598-018-31820-9-
dc.identifier.pmid30201956-
dc.identifier.pmcidPMC6131153-
dc.identifier.scopuseid_2-s2.0-85053203833-
dc.identifier.hkuros299544-
dc.identifier.volume8-
dc.identifier.spagearticle no. 13522-
dc.identifier.epagearticle no. 13522-
dc.identifier.isiWOS:000444086700034-
dc.publisher.placeUnited Kingdom-

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