» Articles » PMID: 39188831

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies

Abstract

Introduction: Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role. C-myc is a proto-oncogene encoding for a nuclear phosphoprotein implicated in cell cycle progression, apoptosis and cellular differentiation and transformation.

Objective: The purpose of the current molecular review was to explore the differences of C-myc oncogenic activity in solid and lymphoid malignancies that modify its clinical impact on them.

Material And Method: A systematic review of the literature in the international database PubMed was carried out. The year 2010 was set as a prominent time limit for the publication date of articles in the majority of them, whereas specific references of great importance and historical value in the field of C-myc gene discovery and analysis were also included. The following keywords were used: C-myc, oncogene, signaling pathway, malignancies, carcinoma, lymphoma. A pool of 43 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies.

Results: C-myc oncogene demonstrates two different mechanisms of deregulation: amplification, mutation and translocation patterns. These particular aspects of gene alteration are unique for solid and non-solid (hematological) malignancies, respectively.

Conclusions: C-myc is characterized by diversity regarding its deregulation mechanisms in malignancies derived from different tissues. C-myc translocation is sporadically combined with amplification ("complicon" formation) or mutations creating exotic genetic signatures. This "bi-phasic" C-myc deregulation model in the corresponding malignant tumor categories clinically affects the corresponding patients, also modifying the targeted therapeutic strategies on them.

Citing Articles

Exosomal ncRNAs in reproductive cancers†.

Kowalczyk A, Wrzecinska M, Galeska E, Czerniawska-Piatkowska E, Camina M, Araujo J Biol Reprod. 2024; 112(2):225-244.

PMID: 39561105 PMC: 11833474. DOI: 10.1093/biolre/ioae170.

References
1.
Grandori C, Cowley S, James L, Eisenman R . The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol. 2000; 16:653-99. DOI: 10.1146/annurev.cellbio.16.1.653. View

2.
Liu C, Ren Q, Deng J, Wang S, Ren L . c-MYC/METTL3/LINC01006 positive feedback loop promotes migration, invasion and proliferation of non-small cell lung cancer. Biomed J. 2023; 47(4):100664. PMC: 11340496. DOI: 10.1016/j.bj.2023.100664. View

3.
Chen G, Chen S, Liu S, Hsieh C, Lee S, Huang S . Stabilization of the c-Myc Protein via the Modulation of Threonine 58 and Serine 62 Phosphorylation by the Disulfiram/Copper Complex in Oral Cancer Cells. Int J Mol Sci. 2022; 23(16). PMC: 9409128. DOI: 10.3390/ijms23169137. View

4.
Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel M . Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas. Leukemia. 2007; 21(3):515-23. DOI: 10.1038/sj.leu.2404529. View

5.
Baeissa H, Benstead-Hume G, Richardson C, Pearl F . Identification and analysis of mutational hotspots in oncogenes and tumour suppressors. Oncotarget. 2017; 8(13):21290-21304. PMC: 5400584. DOI: 10.18632/oncotarget.15514. View