Department of Medical Examination, The Beijing Prevention and Treatment Hospital of Occupational Disease, Beijing 100093, China
| Abstract: | A large number of reports have suggested that the cancer is associated with the gene mutations and chromosomal aberrations, and thus it has been a focus of research. Today new insights are proposed by analyzing relevant literature, suggesting that the cancer is not caused by the gene mutations and chromosomal aberrations, but by the regulatory dysfunction of gene expression resulted from the nuclear damage, among which, the gene mutations and chromosomal aberrations are only an accompany phenomena also resulting from the nuclear damage. The gene mutations generally do not cause diseases, but if they do, they mainly cause the single-gene diseases. The chromosomal aberrations usually refer to the abnormalities in chromosome structure and number, often leading to cell death or inducing various chromosomal diseases. Some chronic refractory diseases, such as the cancer, Alzheimer's disease, degenerative diseases, are probably not caused by the gene mutations and chromosomal abnormalities, but rather by the abnormal regulation of gene expression and the dysfunction of DNA transcription-protein synthesis resulted from the nuclear damage. These diseases are all the diseases of nuclear dysfunction and collapse of differentiation. |
| Keywords: | Gene Mutation; Chromosomal Aberration; Nuclear Dysfunction; Nuclear Damage; Regulation of Gene Expression; Disruption of Differentiation State; Functional Gene; Sealed Gene |
| DOI: | 10.57237/j.mrf.2025.03.001 |
| [1] | Baosheng Yang, Gang Li, Haiyan Jiao, Li Li, Lan Luo, et al. Medical Genetics M, 2rd ed. Higher Education Press. Beijing, China. 2019.01, P12-19. |
| [2] | Rageul J, Kim H. Fanconi anemia and the underlying causes of genomic instability [J]. Environ Mol Mutagen. 2020, 61(7): 693-708. https://doi.org/10.1002/em.22358 |
| [3] | Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, et al. Landscape of genetic infantile epileptic spasms syndrome-A multicenter cohort of 124 children from India [J]. Epilepsia Open. 2023 Dec; 8(4): 1383-1404. https://doi.org/10.1002/epi4.12811 |
| [4] | Ay C, Frenzel L, Pinachyan K, Le Quellec S. Gene therapy for haemophilia A and B, from basic principles to clinical implementation: An illustrated review [J]. Haemophilia. 2024 [J]an; 30(1): 5-15. https://doi.org/10.1111/hae.14907 |
| [5] | Hokland P, Daar S, Khair W, Sheth S, Taher AT, et al. Thalassaemia-A global view [J]. Br J Haematol. 2023 Apr; 201(2): 199-214. https://doi.org/10.1111/bjh.18671 |
| [6] | Chen C, Luo Y, Hou X, Li T. Clinical characterization of epilepsy in children with chromosomal aberration 47, XXY [J]. Brain Behav. 2023 Aug; 13(8): e3178. https://doi.org/10.1002/brb3.3178 |
| [7] | Los E, Leslie SW, Ford GA. Klinefelter Syndrome [J]. 2023 Nov 12. In: StatPearls Internet. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. https://pubmed.ncbi.nlm.nih.gov/29493939/ |
| [8] | Voskarides K, Giannopoulou N. The Role of TP53 in Adaptation and Evolution [J]. Cells. 2023 Feb 3; 12(3): 512. https://doi.org/10.3390/cells12030512 |
| [9] | Ishikawa Y, Ushijima Y, Kiyoi H. Recent advances in AML with mutated NPM1 [J]. Int J Hematol. 2024 Nov; 120(5): 556-565. https://doi.org/10.1007/s12185-024-03835-8 |
| [10] | Ferreira-Marques M, Carvalho A, Franco AC, Leal A, Botelho M, et al. Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome [J]. Aging Cell. 2023 Dec; 22(12): e13983. https://doi.org/10.1111/acel.13983 |
| [11] | Peng L, Baradar AA, Aguado J, Wolvetang E. Cellular senescence and premature aging in Down Syndrome [J]. Mech Ageing Dev. 2023 Jun; 212: 111824. https://doi.org/10.1016/j.mad.2023.111824 |
| [12] | Aragane Y, Higashino T, Kinoshita K, Ashenagar MS, Higashino H. Hypertension-Associated Genes in the Mesenteric Artery of Three Spontaneously Hypertensive Rat Substrains Identified Using a DNA Array Method [J]. Front Biosci (Landmark Ed). 2022 Jun 15; 27(6): 191. https://doi.org/10.31083/j.fbl2706191 |
| [13] | Priviero F. Epigenetic modifications and fetal programming: Molecular mechanisms to control hypertension inheritance [J]. Biochem Pharmacol. 2023 Feb; 208: 115412. https://doi.org/10.1016/j.bcp.2023.115412 |
| [14] | Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications [J]. Nat Rev Nephrol. 2020 Jul; 16(7): 377-390. https://doi.org/10.1038/s41581-020-0278-5 |
| [15] | Bertram L, Tanzi RE. Genomic mechanisms in Alzheimer's disease [J]. Brain Pathol. 2020 Sep; 30(5): 966-977. https://doi.org/10.1111/bpa.12882 |
| [16] | Gholami A. Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches [J]. Neurosci Lett. 2023 Nov 20; 817: 137532. https://doi.org/10.1016/j.neulet.2023.137532 |
| [17] | Freibauer A, Wohlleben M, Boelman C. STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions [J]. Genes (Basel). 2023 Dec 5; 14(12): 2179. https://doi.org/10.3390/genes14122179 |
| [18] | Dominik N, Magri S, Currò R, Abati E, Facchini S, et al. Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis [J]. Brain. 2023 Dec 1; 146(12): 5060-5069. https://doi.org/10.1093/brain/awad240 |
| [19] | Tyagi N, Uppili B, Sharma P, Parveen S, Saifi S, et al. Investigation of RFC1 tandem nucleotide repeat locus in diverse neurodegenerative outcomes in an Indian cohort [J]. Neurogenetics. 2024 Jan; 25(1): 13-25. https://doi.org/10.1007/s10048-023-00736-6 |
| [20] | Vaddavalli PL, Schumacher B. The p53 network: cellular and systemic DNA damage responses in cancer and aging [J]. Trends Genet. 2022 Jun; 38(6): 598-612. https://doi.org/10.1016/j.tig.2022.02.010 |
| [21] | Lim DV, Woo WH, Lim JX, Loh XY, Soh HT, et al. Targeting Mutant-p53 for Cancer Treatment: Are We There Yet? [J] Curr Mol Pharmacol. 2024; 17(1): e140923221042. https://doi.org/10.2174/1874467217666230914090621 |
| [22] | Patel SS. NPM1-Mutated Acute Myeloid Leukemia: Recent Developments and Open Questions [J]. Pathobiology. 2024; 91(1): 18-29. https://doi.org/10.1159/000530253 |
| [23] | Abou Dalle I, Moukalled N, El Cheikh J, Mohty M, Bazarbachi A. Philadelphia-chromosome positive acute lymphoblastic leukemia: ten frequently asked questions [J]. Leukemia. 2024 Sep; 38(9): 1876-1884. https://doi.org/10.1038/s41375-024-02319-2 |
| [24] | Haider MZ, Anwer F. Genetics, Philadelphia Chromosome [J]. 2023 Jul 17. In: StatPearls Internet. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. https://pubmed.ncbi.nlm.nih.gov/32809524/ |
| [25] | Salaverria I, Weigert O, Quintanilla-Martinez L. The clinical and molecular taxonomy of t(14;18)-negative follicular lymphomas [J]. Blood Adv. 2023 Sep 26; 7(18): 5258-5271. https://doi.org/10.1182/bloodadvances.20220.09456 |
| [26] | De Wolf D, Singh K, Chuah MK, Vanden Driessche T. Hemophilia Gene Therapy: The End of the Beginning? [J] Hum Gene Ther. 2023 Sep; 34(17-18): 782-792. https://doi.org/10.1089/hum.2023.112 |
| [27] | Songbin Fu, Feng CHen, Baosheng Yang, Xiaojun Wen, Weiying Jiang. Medical Genetics M, 4rd ed. Peking University Medical Press. Beijing, China. 2018.08, P10-55. |
| [28] | Bhatt S, Argueta DA, Gupta K, Kundu S. Red Blood Cells as Therapeutic Target to Treat Sickle Cell Disease [J]. Antioxid Redox Signal. 2024 Jun; 40(16-18): 1025-1049. https://doi.org/10.1089/ars.2023.0348 |
| [29] | Gupta K, Krishnamurti L, Jain D. Sickle cell disease in India: the journey and hope for the future [J]. Hematology Am Soc Hematol Educ Program. 2024 Dec 6; 2024(1): 1-9. https://doi.org/10.1182/hematology.2024000678 |
| [30] | Pace BS, Starlard-Davenport A, Kutlar A. Sickle cell disease: progress towards combination drug therapy [J]. Br J Haematol. 2021 Jul; 194(2): 240-251. https://doi.org/10.1111/bjh.17312 |
| [31] | Gravholt CH, Viuff M, Just J, Sandahl K, Brun S, et al. The Changing Face of Turner Syndrome [J]. Endocr Rev. 2023 Jan 12; 44(1): 33-69. https://doi.org/10.1210/endrev/bnac016 |
| [32] | Steiner M, Saenger P. Turner Syndrome: An Update [J]. Adv Pediatr. 2022 Aug; 69(1): 177-202. https://doi.org/10.1016/j.yapd.2022.03.004 |
| [33] | Hines CB, Simmons SA. Down Syndrome: A Review of Key Perioperative Implications [J]. AORN J. 2022 Jul; 116(1): 4-20. https://doi.org/10.1002/aorn.13712 |
| [34] | Shaikh A, Li YQ, Lu J. Perspectives on pain in Down syndrome [J]. Med Res Rev. 2023 Sep; 43(5): 1411-1437. https://doi.org/10.1002/med.21954 |
| [35] | Sá R, Ferraz L, Barros A, Sousa M. The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes [J]. Genes (Basel). 2023 Mar 4; 14(3): 647. https://doi.org/10.3390/genes14030647 |
| [36] | Ridder LO, Berglund A, Stochholm K, Chang S, Gravholt CH. Morbidity, mortality, and socioeconomics in Klinefelter syndrome and 47, XYY syndrome: a comparative review [J]. Endocr Connect. 2023 Apr 26; 12(5): e230024. https://doi.org/10.1530/EC-23-0024 |
| [37] | Nickoloff JA, Sharma N, Allen CP, Taylor L, Allen SJ, et al. Roles of homologous recombination in response to ionizing radiation-induced DNA damage [J]. Int J Radiat Biol. 2023; 99(6): 903-914. https://doi.org/10.1080/09553002.2021.1956001 |
| [38] | Zhang L, Richards A, Barrasa MI, Hughes SH, Young RA, et al. Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues [J]. Proc Natl Acad Sci U S A. 2021 May 25; 118(21): e2105968118. https://doi.org/10.1073/pnas.2105968118 |
| [39] | Auschwitz E, Almeda J, Andl CD. Mechanisms of E-Cigarette Vape-Induced Epithelial Cell Damage [J]. Cells. 2023 Oct 31; 12(21): 2552. https://doi.org/10.3390/cells12212552 |
| [40] | Barbosa F Jr, Rocha BA, Souza MCO, Bocato MZ, Azevedo LF, et al. Polycyclic aromatic hydrocarbons (PAHs): Updated aspects of their determination, kinetics in the human body, and toxicity [J]. J Toxicol Environ Health B Crit Rev. 2023 Jan 2; 26(1): 28-65. https://doi.org/10.1080/10937404.2022.2164390 |
| [41] | Ortega Pijeira MS, Magne TM, da Silva NCG, Ramos Ribeiro ERF, Albuquerque Silva YJ, et al. Ionizing Radiation: Chemical Kinetics, Chemical Bounds, and Radiation Chemistry on Polymers [J]. Curr Top Med Chem. 2023; 23(15): 1414-1424. https://doi.org/10.2174/1568026623666230315122855 |
| [42] | Al-Jumayli M, Brown SL, Chetty IJ, Extermann M, Movsas B. The Biological Process of Aging and the Impact of Ionizing Radiation [J]. Semin Radiat Oncol. 2022 Apr; 32(2): 172-178. https://doi.org/10.1016/j.semradonc.2021.11.011 |
| [43] | Falini B. NPM1-mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions [J]. Am J Hematol. 2023 Sep; 98(9): 1452-1464. https://doi.org/10.1002/ajh.26989 |
| [44] | Dietlein F, Wang AB, Fagre C, Tang A, Besselink NJM, et al. Genome-wide analysis of somatic noncoding mutation patterns in cancer [J]. Science. 2022 Apr 8; 376(6589): eabg5601. https://doi.org/10.1126/science.abg5601 |
| [45] | Dougherty JA, Dougherty KM. Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene Therapies for Hemophilia A and B [J]. Ann Pharmacother. 2024 Aug; 58(8): 834-848. https://doi.org/10.1177/10600280231202247 |
| [46] | Wang WD, Hu F, Zhou DH, Gale RP, Lai YR, et al. Thalassaemia in China [J]. Blood Rev. 2023 Jul; 60: 101074. https://doi.org/10.1016/j.blre.2023.101074 |
| [47] | Mogensen TH. Genetic susceptibility to viral disease in humans [J]. Clin Microbiol Infect. 2022 Nov; 28(11): 1411-1416. https://doi.org/10.1016/j.cmi.2022.02.023 |
| [48] | Maojin Li, Anyi H. The research progress and biological significance of abnormality nuclear of cell nucleus [J]. Chin Occup Med, 2021, 48(6): 708-711. https://doi.org/10.20001/j.issn.2095-2619.20211995 |
| [49] | Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia [J]. Lancet. 2022 Jun 18; 399(10343): 2310-2324. https://doi.org/10.1016/S0140-6736(22)00536-0 |
| [50] | Elendu C, Amaechi DC, Alakwe-Ojimba CE, Elendu TC, Elendu RC, et al. Understanding Sickle cell disease: Causes, symptoms, and treatment options [J]. Medicine (Baltimore). 2023 Sep 22; 102(38): e35237. https://doi.org/10.1097/MD.0000000000035237 |
| [51] | Samelson-Jones BJ, Small JC, George LA. Roctavian gene therapy for hemophilia A [J]. Blood Adv. 2024 Oct 8; 8(19): 5179-5189. https://doi.org/10.1182/bloodadvances.2023011847 |
| [52] | Dashti P, van de Peppel J, Thaler R, Paradise CR, Stein GS, et al. The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and Enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization [J]. Gene. 2023 Jan 30; 851: 146928. https://doi.org/10.1016/j.gene.2022.146928 |
| [53] | Dashti P, Lewallen EA, Gordon JAR, Montecino MA, van Leeuwen JPTM, et al. Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation [J]. Bone Rep. 2023 Jul 25; 19: 101704. https://doi.org/10.1016/j.bonr.2023.101704 |
| [54] | Zhang QQ, Qu Y. Brain-derived neurotrophic factor in degenerative retinal diseases: Update and novel perspective [J]. J Neurosci Res. 2023 Oct; 101(10): 1624-1632. https://doi.org/10.1002/jnr.25226 |
| [55] | Han TS, Kim DS, Son MY, Cho HS. SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance [J]. Exp Mol Med. 2024 Nov; 56(11): 2325-2336. https://doi.org/10.1038/s12276-024-01326-8 |
| [56] | Thejer BM, Infantino V, Santarsiero A, Pappalardo I, Abatematteo FS, et al. Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97 [J]. Int J Mol Sci. 2023 Mar 28; 24(7): 6381. https://doi.org/10.3390/ijms24076381 |
| [57] | Padilla A, Manganaro JF, Huesgen L, Roess DA, Brown MA, et al. Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases [J]. Molecules. 2023 Feb 20; 28(4): 2000. https://doi.org/10.3390/molecules28042000 |
| [58] | Skinner MK. Epigenetic biomarkers for disease susceptibility and preventative medicine [J]. Cell Metab. 2024 Feb 6; 36(2): 263-277. https://doi.org/10.1016/j.cmet.2023.11.015 |
| [59] | Chaudhary MR, Chaudhary S, Sharma Y, Singh TA, Mishra AK, et al. Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies [J]. Biogerontology. 2023 Oct; 24(5): 609-662. https://doi.org/10.1007/s10522-023-10050-1 |
| [60] | Lizama BN, Kahle J, Catalano SM, Caggiano AO, Grundman M, et al. Sigma-2 Receptors-From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases [J]. Int J Mol Sci. 2023 Mar 26; 24(7): 6251. https://doi.org/10.3390/ijms24076251 |
| [61] | Kruseova J, Zichova A, Eckschlager T. Premature aging in childhood cancer survivors [J]. Oncol Lett. 2022 Dec 13; 25(2): 43. https://doi.org/10.3892/ol.2022.13629 |
| [62] | Ma Z, Chen L, Wang Y, Zhang S, Zheng J, et al. Novel insights of EZH2-mediated epigenetic modifications in degenerative musculoskeletal diseases [J]. Ageing Res Rev. 2023 Sep; 90: 102034. https://doi.org/10.1016/j.arr.2023.102034 |
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