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Current Alzheimer Research

Author(s): Yong-Chan Kim and Byung-Hoon Jeong*

DOI: 10.2174/1567205017666201203124341

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Identification of Somatic Mutations in Dementia-related Genes in Cancer Patients

Page: [835 - 844] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: Dementia is an overall term of brain diseases, including Alzheimer’s disease (AD), tauopathies and synucleinopathies. To date, somatic mutations in dementia-related genes, including the amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene, PSEN2 gene, microtubule- associated protein tau (MAPT) gene, alpha-synuclein (SNCA) gene and leucine-rich repeat kinase 2 (LRRK2) gene, have been considered one cause of dementia. We have questioned the impact of somatic mutations in dementia-related genes on cancer.

Methods: In the present study, we investigated somatic mutations in the APP, PSEN1, PSEN2, MAPT, SNCA and LRRK2 genes and the impact of these somatic mutations.

Results: From The Cancer Genome Atlas (TCGA) database, we found 1,643 somatic mutations in the APP, PSEN1, PSEN2, MAPT, SNCA and LRRK2 genes in cancer patients. Strikingly, compared to the distributions of cancer types in total cancer patients, somatic mutations in the dementia-related genes showed an extremely low distribution in glioblastoma patients.

Conclusion: To the best of our knowledge, this is the first investigation of dementia-related genes in cancer patients.

Keywords: Somatic mutation, dementia, APP, PSEN1, PSEN2, MAPT, SNCA, LRRK2, glioblastoma.

[1]
Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: Review JAMA 2019; 322(16): 1589-99.
[http://dx.doi.org/10.1001/jama.2019.4782 ] [PMID: 31638686]
[2]
Stokes L, Combes H, Stokes G. The dementia diagnosis: A literature review of information, understanding, and attributions. Psychogeriatrics 2015; 15(3): 218-25.
[http://dx.doi.org/10.1111/psyg.12095 ] [PMID: 25515569]
[3]
Weggen S, Beher D. Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer’s disease. Alzheimers Res Ther 2012; 4(2): 9.
[http://dx.doi.org/10.1186/alzrt107 ] [PMID: 22494386]
[4]
Lanoiselée HM, Nicolas G, Wallon D, et al. Collaborators of the CNR-MAJ project. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med 2017; 14(3)e1002270
[http://dx.doi.org/10.1371/journal.pmed.1002270 ] [PMID: 28350801]
[5]
Kelleher RJ III, Shen J. Presenilin-1 mutations and Alzheimer’s disease. Proc Natl Acad Sci USA 2017; 114(4): 629-31.
[http://dx.doi.org/10.1073/pnas.1619574114 ] [PMID: 28082723]
[6]
Götz J, Halliday G, Nisbet RM. Molecular pathogenesis of the tauopathies. Annu Rev Pathol 2019; 14: 239-61.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012936 ] [PMID: 30355155]
[7]
Orr ME, Sullivan AC, Frost B. A brief overview of tauopathy: Causes, consequences, and therapeutic strategies. Trends Pharmacol Sci 2017; 38(7): 637-48.
[http://dx.doi.org/10.1016/j.tips.2017.03.011 ] [PMID: 28455089]
[8]
Kim YC, Jeong BH. In silico evaluation of acetylation mimics in the 27 lysine residues of human tau protein. Curr Alzheimer Res 2019; 16(5): 379-87.
[http://dx.doi.org/10.2174/1567205016666190321161032 ] [PMID: 30907318]
[9]
Konno T, Siuda J, Wszolek ZK. Genetics of Parkinson’s disease: A review of SNCA and LRRK2. Wiad Lek 2016; 69(3 Pt 1): 328-32.
[PMID: 27486710]
[10]
Campêlo CLDC, Silva RH. Genetic variants in SNCA and the risk of sporadic Parkinson’s disease and clinical outcomes: A review. Parkinsons Dis 2017; 20174318416
[http://dx.doi.org/10.1155/2017/4318416 ] [PMID: 28781905]
[11]
Bird TD. $arly-onset familial alzheimer disease. GeneReviews. Seattle, WA 1993. Vol. R.
[12]
Momeni P, Wickremaratchi MM, Bell J, et al. Familial early onset frontotemporal dementia caused by a novel S356T MAPT mutation, initially diagnosed as schizophrenia. Clin Neurol Neurosurg 2010; 112(10): 917-20.
[http://dx.doi.org/10.1016/j.clineuro.2010.07.015 ] [PMID: 20708332]
[13]
Iqbal K, Liu F, Gong CX, Grundke-Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res 2010; 7(8): 656-64.
[http://dx.doi.org/10.2174/156720510793611592 ] [PMID: 20678074]
[14]
Alzualde A, Moreno F, Martínez-Lage P, et al. Somatic mosaicism in a case of apparently sporadic Creutzfeldt-Jakob disease carrying a de novo D178N mutation in the PRNP gene. Am J Med Genet B Neuropsychiatr Genet 2010; 153B(7): 1283-91.
[http://dx.doi.org/10.1002/ajmg.b.31099 ] [PMID: 20872767]
[15]
Dagvadorj A, Petersen RB, Lee HS, et al. Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy. Ann Neurol 2002; 52(3): 355-9.
[http://dx.doi.org/10.1002/ana.10267 ] [PMID: 12205650]
[16]
Leija-Salazar M, Piette C, Proukakis C. Review: Somatic mutations in neurodegeneration. Neuropathol Appl Neurobiol 2018; 44(3): 267-85.
[http://dx.doi.org/10.1111/nan.12465 ] [PMID: 29369391]
[17]
Nicolas G, Veltman JA. The role of de novo mutations in adult-onset neurodegenerative disorders. Acta Neuropathol 2019; 137(2): 183-207.
[http://dx.doi.org/10.1007/s00401-018-1939-3 ] [PMID: 30478624]
[18]
Erickson RP. Somatic gene mutation and human disease other than cancer. Mutat Res 2003; 543(2): 125-36.
[http://dx.doi.org/10.1016/S1383-5742(03)00010-3 ] [PMID: 12644182]
[19]
Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol 2010; 11(3): 220-8.
[http://dx.doi.org/10.1038/nrm2858 ] [PMID: 20177397]
[20]
Shen Z. Genomic instability and cancer: An introduction. J Mol Cell Biol 2011; 3(1): 1-3.
[http://dx.doi.org/10.1093/jmcb/mjq057 ] [PMID: 21278445]
[21]
Silva JL, Rangel LP, Costa DC, Cordeiro Y, De Moura Gallo CV. Expanding the prion concept to cancer biology: Dominant-negative effect of aggregates of mutant p53 tumour suppressor. Biosci Rep 2013; 33(4)e00054
[http://dx.doi.org/10.1042/BSR20130065 ] [PMID: 24003888]
[22]
Tomczak K, Czerwińska P, Wiznerowicz M. The cancer genome atlas (TCGA): An immeasurable source of knowledge. Contemp Oncol (Pozn) 2015; 19(1A): A68-77.
[http://dx.doi.org/10.5114/wo.2014.47136 ] [PMID: 25691825]
[23]
Kim YC, Kim SK, Jeong BH. Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats. Sci Rep 2019; 9(1): 15261.
[http://dx.doi.org/10.1038/s41598-019-51625-8 ] [PMID: 31649311]
[24]
Kim SK, Kim YC, Won SY, Jeong BH. Potential scrapie-associated polymorphisms of the prion protein gene (PRNP) in Korean native black goats. Sci Rep 2019; 9(1): 15293.
[http://dx.doi.org/10.1038/s41598-019-51621-y ] [PMID: 31653880]
[25]
Jeong BH, Kim YS. Genetic studies in human prion diseases. J Korean Med Sci 2014; 29(5): 623-32.
[http://dx.doi.org/10.3346/jkms.2014.29.5.623 ] [PMID: 24851016]
[26]
Lloyd S, Mead S, Collinge J. Genetics of prion disease. Top Curr Chem 2011; 305: 1-22.
[http://dx.doi.org/10.1007/128_2011_157 ] [PMID: 21528440]
[27]
Won SY, Kim YC, Jeong BH. First report of the potential bovine spongiform encephalopathy (BSE)-related somatic mutation E211K of the prion protein gene (PRNP) in cattle. Int J Mol Sci 2020; 21(12): 4246.
[http://dx.doi.org/10.3390/ijms21124246 ] [PMID: 32549191]
[28]
Lalonde R, Fukuchi K, Strazielle C. APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD). Neurosci Biobehav Rev 2012; 36(5): 1357-75.
[http://dx.doi.org/10.1016/j.neubiorev.2012.02.011 ] [PMID: 22373961]
[29]
Sasaguri H, Nilsson P, Hashimoto S, et al. APP mouse models for Alzheimer’s disease preclinical studies. EMBO J 2017; 36(17): 2473-87.
[http://dx.doi.org/10.15252/embj.201797397 ] [PMID: 28768718]
[30]
Denk F, Wade-Martins R. Knock-out and transgenic mouse models of tauopathies. Neurobiol Aging 2009; 30(1): 1-13.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.05.010 ] [PMID: 17590238]
[31]
Ninkina N, Connor-Robson N, Ustyugov AA, Tarasova TV, Shelkovnikova TA, Buchman VL. A novel resource for studying function and dysfunction of α-synuclein: Mouse lines for modulation of endogenous Snca gene expression. Sci Rep 2015; 5: 16615.
[http://dx.doi.org/10.1038/srep16615 ] [PMID: 26564109]
[32]
Pasalar P, Najmabadi H, Noorian AR, et al. An Iranian family with Alzheimer’s disease caused by a novel APP mutation (Thr714Ala). Neurology 2002; 58(10): 1574-5.
[http://dx.doi.org/10.1212/WNL.58.10.1574 ] [PMID: 12034808]
[33]
Houlden H, Crook R, Dolan RJ, McLaughlin J, Revesz T, Hardy J. A novel presenilin mutation (M233V) causing very early onset Alzheimer’s disease with Lewy bodies. Neurosci Lett 2001; 313(1-2): 93-5.
[http://dx.doi.org/10.1016/S0304-3940(01)02254-6 ] [PMID: 11684347]
[34]
Yagi R, Miyamoto R, Morino H, Izumi Y, Kuramochi M, Kurashige T, et al. Detecting gene mutations in Japanese Alzheimer’s patients by semiconductor sequencing. Neurobiol Aging 2014; 35(7): e1-5.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.023]
[35]
Thul PJ, Lindskog C. The human protein atlas: A spatial map of the human proteome. Protein Sci 2018; 27(1): 233-44.
[http://dx.doi.org/10.1002/pro.3307 ] [PMID: 28940711]
[36]
Rossi G, Redaelli V, Contiero P, et al. Tau mutations serve as a novel risk factor for cancer. Cancer Res 2018; 78(13): 3731-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3175 ] [PMID: 29794074]
[37]
Rossi G, Redaelli V, Perego P, Ferrari R, Giaccone G, Tagliavini F. Tau mutations as a novel risk factor for cancer-response. Cancer Res 2018; 78(22): 6525.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2730 ] [PMID: 30373808]
[38]
Galvão F Jr, Grokoski KC, da Silva BB, Lamers ML, Siqueira IR. The amyloid precursor protein (APP) processing as a biological link between Alzheimer’s disease and cancer. Ageing Res Rev 2019; 49: 83-91.
[http://dx.doi.org/10.1016/j.arr.2018.11.007 ] [PMID: 30500566]
[39]
Mullin S, Schapira A. α-Synuclein and mitochondrial dysfunction in Parkinson’s disease. Mol Neurobiol 2013; 47(2): 587-97.
[http://dx.doi.org/10.1007/s12035-013-8394-x ] [PMID: 23361255]
[40]
Hafner Bratkovič I. Prions, prionoid complexes and amyloids: The bad, the good and something in between. Swiss Med Wkly 2017; 147w14424
[PMID: 28421568]
[41]
Jaunmuktane Z, Brandner S. Invited Review: The role of prion-like mechanisms in neurodegenerative diseases. Neuropathol Appl Neurobiol 2020; 46(6): 522-45.
[PMID: 31868945]
[42]
Rangel LP, Costa DC, Vieira TC, Silva JL. The aggregation of mutant p53 produces prion-like properties in cancer. Prion 2014; 8(1): 75-84.
[http://dx.doi.org/10.4161/pri.27776 ] [PMID: 24509441]
[43]
Kim YC, Won SY, Jeong BH. Identification of prion disease-related somatic mutations in the prion protein gene (PRNP) in cancer patients. Cells 2020; 9(6): 1480.
[http://dx.doi.org/10.3390/cells9061480] [PMID: 32560489]