Molecular characterization of multiple myeloma

Authors

  • B. Zeren Kiremitci Department of Genetics and Bioengineering, İzmir University of Economics, İzmir, Turkey
  • Elif Serap Gürler Department of Genetics and Bioinformatics, Kadir Has University, İstanbul, Turkey
  • Yağmur Kiraz Department of Genetics and Bioengineering, İzmir University of Economics, İzmir, Turkey https://orcid.org/0000-0003-3508-5617

DOI:

https://doi.org/10.20883/medical.e656

Keywords:

multiple myeloma, KRAS, NRAS, mutations

Abstract

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.

Downloads

Download data is not yet available.

References

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. DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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. DOI: https://doi.org/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. DOI: https://doi.org/10.1158/2159-8290.CD-12-0095

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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/10.1038/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/10.1093/nar/gkp936

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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/10.1038/s41388-019-1037-6

How to Cite

1.
Kiremitci BZ, Gürler ES, Kiraz Y. Molecular characterization of multiple myeloma. JMS [Internet]. 2022 Jul. 7 [cited 2022 Aug. 10];91(2):e656. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/656

Issue

Section

Review Papers
Received 2022-04-28
Accepted 2022-06-30
Published 2022-07-07