Molecular characterization of multiple myeloma
DOI:
https://doi.org/10.20883/medical.e656Keywords:
multiple myeloma, KRAS, NRAS, mutationsAbstract
Multiple myeloma (MM) is a hematologic malignancy which occurs when plasma cells, a type of white blood cell, grow out of control and start to overproduce antibodies accumulating in the blood and bone marrow. Despite the recent advances, the survival rate for MM has not increased significantly which opens the need for identifying new molecular targets. This review article presents the most frequently observed gene mutations (KRAS (22.0%), NRAS (18.0%), DIS3 (9.3%), TTN (8.3%), ZNF717 (8.3%), TENT5C (7.3%), TP53 (7.3%) %), BRAF (6.3%), MUC16 (6.3%), RYR2 (5.4%), and LRP1B (5.4%)) in MM patients, with their rates, correlations, clinical significance, importance in the framework of MM, as well as potential novel targets collected from the literature. The genes and MM patients’ dataset (211) were obtained from cBioportal. Summing up, in the study conducted in MM patients, 3 genes with the most frequent mutations were reported as KRAS, NRAS and DIS3. In addition, in the context of our literature reviews and the data obtained, it appears that the TZNF717, TTN, MUC16, RYR2 genes need further investigations within the framework of MM.
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Zhou Y, Barlogie B, Shaughnessy JD Jr. The molecular characterization and clinical management of multiple myeloma in the post-genome era. Leukemia. 2009 Nov;23(11):1941–56. . doi: 10.1038/leu.2009.160.
Rajkumar SV, Kumar S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc. 2016 Jan;91(1):101–19. doi: 10.1016/j.mayocp.2015.11.007
Röllig C, Knop S, Bornhäuser M. Multiple myeloma [Internet]. Vol. 385, The Lancet. 2015. p. 2197–208. Available from: http://dx.doi.org/10.1016/s0140-6736(14)60493-1
Mitsiades CS, Mitsiades N, Munshi NC, Anderson KC. Focus on multiple myeloma. Cancer Cell. 2004 Nov;6(5):439–44. doi: 10.1016/j.ccr.2004.10.020
Braggio E, Kortüm KM, Stewart AK. SnapShot: Multiple Myeloma. Cancer Cell. 2015 Nov 9;28(5):678–678.e1. doi: 10.1016/j.ccell.2015.10.014
Key statistics for multiple myeloma [Internet]. [cited 2021 Dec 31]. Available from: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html
Ashcroft AJ, Davies FE, Morgan GJ. Aetiology of bone disease and the role of bisphosphonates in multiple myeloma. Lancet Oncol. 2003 May;4(5):284–92. doi: 10.1016/S1470-2045(03)01076-3
Anderson KC. Progress and Paradigms in Multiple Myeloma. Clin Cancer Res. 2016 Nov 15;22(22):5419–27. doi: 10.1158/1078-0432.CCR-16-0625
Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014 Jan 13;25(1):91–101. doi: 10.1016/j.ccr.2013.12.015
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013 Apr 2;6(269):pl1. doi: 10.1126/scisignal.2004088.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012 May;2(5):401-4. doi: 10.1158/2159-8290.CD-12-0095. Erratum in: Cancer Discov. 2012 Oct;2(10):960.
Szklarczyk D;Gable AL;Nastou KC;Lyon D;Kirsch R;Pyysalo S;Doncheva NT;Legeay M;Fang T;Bork P;Jensen LJ;von Mering C; The string database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets [Internet]. Nucleic acids research. U.S. National Library of Medicine; [cited 2022Apr27]. Available from: https://pubmed.ncbi.nlm.nih.gov/33237311/ doi: 10.1093/nar/gkaa1074
Jelinek T, Paiva B, Hajek R. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma. Front Immunol. 2018 Nov 16; 9:2431. doi: 10.3389/fimmu.2018.02431
Pasca S, Tomuleasa C, Teodorescu P, Ghiaur G, Dima D, Moisoiu V, et al. KRAS/NRAS/BRAF Mutations as Potential Targets in Multiple Myeloma. Front Oncol. 2019 Oct 24;9:1137. doi: 10.3389/fonc.2019.01137
Kortüm KM, Langer C, Monge J, Bruins L, Egan JB, Zhu YX, et al. Targeted sequencing using a 47 gene multiple myeloma mutation panel (M(3) P) in -17p high risk disease. Br J Haematol. 2015 Feb;168(4):507–10. doi: 10.1111/bjh.13171
Dutta AK, Fink JL, Grady JP, Morgan GJ, Mullighan CG, To LB, et al. Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability. Leukemia. 2019 Feb;33(2):457–68. doi: 10.1038/s41375-018-0206-x
Stelzer G, Rosen R, Plaschkes I, Zimmerman S, Twik M, Fishilevich S et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analysis, Current Protocols in Bioinformatics(2016), 54:1.30.1 - 1.30.33. doi: 10.1002/cpbi.5
Griffith M*,†, Spies NC*, Krysiak K*, McMichael JF, Coffman AC, Danos AM et al. 2016. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 49, 170–174 (2017); doi: doi.org/10.1038/ng.3774
National Center for Biotechnology Information (NCBI)[Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; [1988] – [cited 2017 Apr 06]. Available from: https://www.ncbi.nlm.nih.gov/
Hu Y, Chen W, Wang J. Progress in the identification of gene mutations involved in multiple myeloma. Onco Targets Ther. 2019 May 24; 12:4075–80. doi: 10.2147/OTT.S205922
Boyle EM, Ashby C, Tytarenko RG, Deshpande S, Wang H, Wang Y, et al. BRAF and DIS3 Mutations Associate with Adverse Outcome in a Long-term Follow-up of Patients with Multiple Myeloma. Clin Cancer Res. 2020 May 15;26(10):2422–32. doi: 10.1158/1078-0432.CCR-19-1507
Corre J, Cleynen A, Robiou du Pont S, Buisson L, Bolli N, Attal M, et al. Multiple myeloma clonal evolution in homogeneously treated patients. Leukemia. 2018 Dec;32(12):2636–47. doi: 0.1038/s41375-018-0153-6
Li B, Liu C, Cheng G, Peng M, Qin X, Liu Y, et al. LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population. J Cancer. 2019 Jan 1;10(3):577–82. doi: 10.7150/jca.28905
Zhu YX, Shi C-X, Bruins LA, Jedlowski P, Wang X, Kortüm KM, et al. Loss of FAM46C Promotes Cell Survival in Myeloma. Cancer Res. 2017 Aug 15;77(16):4317–27. doi: 10.1158/0008-5472.CAN-16-3011
Herrero AB, Quwaider D, Corchete LA, Mateos MV, García-Sanz R, Gutiérrez NC. FAM46C controls antibody production by the polyadenylation of immunoglobulin mRNAs and inhibits cell migration in multiple myeloma. J Cell Mol Med. 2020 Apr;24(7):4171–82. doi: 10.1111/jcmm.15078
Jovanović KK, Escure G, Demonchy J, Willaume A, Van de Wyngaert Z, Farhat M, et al. Deregulation and Targeting of TP53 Pathway in Multiple Myeloma. Front Oncol. 2018;8:665. doi: 10.3389/fonc.2018.00665
Kapushesky M, Emam I, Holloway E, Kurnosov P, Zorin A, Malone J, et al. Gene expression atlas at the European bioinformatics institute. Nucleic Acids Res. 2010 Jan;38 (Database issue): D690-8. doi: 10.1093/nar/gkp936. Available from: https://www.ebi.ac.uk/gxa/home
Chauveau C, Rowell J, Ferreiro A. A rising titan: TTN review and mutation update. Hum Mutat. 2014 Sep;35(9):1046–59. doi: 10.1002/humu.22611
Wang Z, Wang C, Lin S, Yu X. Effect of TTN Mutations on Immune Microenvironment and Efficacy of Immunotherapy in Lung Adenocarcinoma Patients. Front Oncol. 2021 Aug 26;11:725292. doi: 10.3389/fonc.2021.725292
Duan M, Hao J, Cui S, Worthley DL, Zhang S, Wang Z, et al. Diverse modes of clonal evolution in HBV-related hepatocellular carcinoma revealed by single-cell genome sequencing [Internet]. Cell research. Nature Publishing Group; 2018 [cited 2022Apr27]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835770/ doi: 10.1038/cr.2018.11
Ye C-Y, Zheng C-P, Ying W-W, Weng S-S. Up-regulation of microRNA-497 inhibits the proliferation, migration and invasion but increases the apoptosis of multiple myeloma cells through the MAPK/ERK signaling pathway by targeting Raf-1. Cell Cycle. 2018 Dec 17;17(24):2666–83. doi: 10.1080/15384101.2018.1542895
Xie Y, Liu J, Jiang H, Wang J, Li X, Wang J, et al. Proteasome inhibitor induced SIRT1 deacetylates GLI2 to enhance hedgehog signaling activity and drug resistance in multiple myeloma. Oncogene. 2020 Jan;39(4):922–34. doi: 10.1038/s41388-019-1037-6
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