Widespread mutagenesis and chromosomal instability shape somatic genomes in systemic sclerosis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
06
04
2024
accepted:
09
10
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
Systemic sclerosis is a connective tissue disorder characterized by excessive fibrosis that primarily affects women, and can present as a multisystem pathology. Roughly 4-22% of patients with systemic sclerosis develop cancer, which drastically worsens prognosis. However, the mechanisms underlying systemic sclerosis initiation, propagation, and cancer development are poorly understood. We hypothesize that the inflammation and immune response associated with systemic sclerosis can trigger DNA damage, leading to elevated somatic mutagenesis, a hallmark of pre-cancerous tissues. To test our hypothesis, we culture clonal lineages of fibroblasts from the lung tissues of controls and systemic sclerosis patients and compare their mutation burdens and spectra. We find an overall increase in all major mutation types in systemic sclerosis samples compared to control lung samples, from small-scale events such as single base substitutions and insertions/deletions, to chromosome-level changes, including copy-number changes and structural variants. In the genomes of patients with systemic sclerosis, we find evidence of somatic hypermutation or kategis (typically only seen in cancer genomes), we identify mutation signatures closely resembling the error-prone translesion polymerase Polη activity, and observe an activation-induced deaminase-like mutation signature, which overlaps with genomic regions displaying kataegis.
Identifiants
pubmed: 39406724
doi: 10.1038/s41467-024-53332-z
pii: 10.1038/s41467-024-53332-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8889Informations de copyright
© 2024. The Author(s).
Références
Peoples, C., Medsger, T. A. Jr., Lucas, M., Rosario, B. L. & Feghali-Bostwick, C. A. Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes. J. Scleroderma Relat. Disord. 1, 177–240 (2016).
pubmed: 29242839
Fan, Y., Bender, S., Shi, W. & Zoz, D. Incidence and prevalence of systemic sclerosis and systemic sclerosis with interstitial lung disease in the United States. J. Manag Care Spec. Pharm. 26, 1539–1547 (2020).
pubmed: 32996805
Ferri, C. et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine 81, 139–153 (2002).
pubmed: 11889413
doi: 10.1097/00005792-200203000-00004
Scussel-Lonzetti, L. et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Med. (Baltim.) 81, 154–167 (2002).
doi: 10.1097/00005792-200203000-00005
Meier, F. M. et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann. Rheum. Dis. 71, 1355–1360 (2012).
pubmed: 22615460
doi: 10.1136/annrheumdis-2011-200742
Varga, J. & Abraham, D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J. Clin. Invest. 117, 557–567 (2007).
pubmed: 17332883
pmcid: 1804347
doi: 10.1172/JCI31139
Barsotti, S. et al. One year in review 2019: systemic sclerosis. Clin. Exp. Rheumatol. 37, 3–14 (2019).
pubmed: 31587697
Volkmann, E. R. & Fischer, A. Update on morbidity and mortality in systemic sclerosis-related interstitial lung disease. J. Scleroderma Relat. Disord. 6, 11–20 (2021).
pubmed: 33693057
doi: 10.1177/2397198320915042
Tyndall, A. J. et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann. Rheum. Dis. 69, 1809–1815 (2010).
pubmed: 20551155
doi: 10.1136/ard.2009.114264
Rubio-Rivas, M., Royo, C., Simeon, C. P., Corbella, X. & Fonollosa, V. Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Semin Arthritis Rheum. 44, 208–219 (2014).
pubmed: 24931517
doi: 10.1016/j.semarthrit.2014.05.010
McNearney, T. A. et al. Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors. Arthritis Rheum. 57, 318–326 (2007).
pubmed: 17330281
doi: 10.1002/art.22532
Steen, V. D. & Medsger, T. A. Changes in causes of death in systemic sclerosis, 1972-2002. Ann. Rheum. Dis. 66, 940–944 (2007).
pubmed: 17329309
pmcid: 1955114
doi: 10.1136/ard.2006.066068
Mouawad, J. E. & Feghali-Bostwick, C. The molecular mechanisms of systemic sclerosis-associated lung fibrosis. Int. J. Mol. Sci. 24 (2023).
Rueda, B. et al. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum. Mol. Genet. 18, 2071–2077 (2009).
pubmed: 19286670
doi: 10.1093/hmg/ddp119
Tsuchiya, N. et al. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann. Rheum. Dis. 68, 1375–1376 (2009).
pubmed: 19605749
doi: 10.1136/ard.2009.111310
Xu, Y., Wang, W., Tian, Y., Liu, J. & Yang, R. Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis. Int J. Dermatol. 55, 408–416 (2016).
pubmed: 26712637
doi: 10.1111/ijd.12839
Dieude, P. et al. Phenotype-haplotype correlation of IRF5 in systemic sclerosis: role of 2 haplotypes in disease severity. J. Rheumatol. 37, 987–992 (2010).
pubmed: 20231204
doi: 10.3899/jrheum.091163
Lafyatis, R. Transforming growth factor beta-at the centre of systemic sclerosis. Nat. Rev. Rheumatol. 10, 706–719 (2014).
pubmed: 25136781
doi: 10.1038/nrrheum.2014.137
Morris, E. et al. Endoglin promotes TGF-beta/Smad1 signaling in scleroderma fibroblasts. J. Cell Physiol. 226, 3340–3348 (2011).
pubmed: 21344387
pmcid: 3381731
doi: 10.1002/jcp.22690
Herrmann, K., Heckmann, M., Kulozik, M., Haustein, U. F. & Krieg, T. Steady-state mRNA levels of collagens I, III, fibronectin, and collagenase in skin biopsies of systemic sclerosis patients. J. Invest. Dermatol. 97, 219–222 (1991).
pubmed: 1649227
doi: 10.1111/1523-1747.ep12480157
Garabrant, D. H. et al. Scleroderma and solvent exposure among women. Am. J. Epidemiol. 157, 493–500 (2003).
pubmed: 12631538
doi: 10.1093/aje/kwf223
Muntyanu, A. et al. Exposure to silica and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group. Front Med. 9, 984907 (2022).
doi: 10.3389/fmed.2022.984907
Shivakumar, D. S., Kamath, N. S. & Naik, A. Silica associated systemic sclerosis: an occupational health hazard. BMJ Case Rep. 16 (2023).
Lescoat, A. et al. Silica exposure and scleroderma: more bridges and collaboration between disciplines are needed. Am. J. Respir. Crit. Care Med. 201, 880–882 (2020).
pubmed: 31881815
pmcid: 7124714
doi: 10.1164/rccm.201911-2218LE
Garrett, S. M., Baker Frost, D. & Feghali-Bostwick, C. The mighty fibroblast and its utility in scleroderma research. J. Scleroderma Relat. Disord. 2, 69–134 (2017).
pubmed: 29270465
Morrisroe, K. & Nikpour, M. Cancer and scleroderma: recent insights. Curr. Opin. Rheumatol. 32, 479–487 (2020).
pubmed: 33002949
doi: 10.1097/BOR.0000000000000755
Zhang, J. Q. et al. The risk of cancer development in systemic sclerosis: a meta-analysis. Cancer Epidemiol. 37, 523–527 (2013).
pubmed: 23725641
doi: 10.1016/j.canep.2013.04.014
Onishi, A., Sugiyama, D., Kumagai, S. & Morinobu, A. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum. 65, 1913–1921 (2013).
pubmed: 23576072
doi: 10.1002/art.37969
Christenson, L. J. et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 294, 681–690 (2005).
pubmed: 16091570
doi: 10.1001/jama.294.6.681
Weeding, E., Casciola-Rosen, L. & Shah, A. A. Cancer and Scleroderma. Rheum. Dis. Clin. North Am. 46, 551–564 (2020).
pubmed: 32631603
pmcid: 7340850
doi: 10.1016/j.rdc.2020.03.002
Bonifazi, M. et al. Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies. Rheumatology 52, 143–154 (2013).
pubmed: 23175568
doi: 10.1093/rheumatology/kes303
Lepri, G. et al. Systemic Sclerosis Association with Malignancy. Clin. Rev. Allergy Immunol. 63, 398–416 (2022).
pubmed: 36121543
pmcid: 9674744
doi: 10.1007/s12016-022-08930-4
Mecoli, C. A., Rosen, A., Casciola-Rosen, L. & Shah, A. A. Advances at the interface of cancer and systemic sclerosis. J. Scleroderma Relat. Disord. 6, 50–57 (2021).
pubmed: 34124375
doi: 10.1177/2397198320905983
Hoffmann-Vold, A. M. et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete nationwide cohort. Am. J. Respir. Crit. Care Med. 200, 1258–1266 (2019).
pubmed: 31310156
doi: 10.1164/rccm.201903-0486OC
Pezone, A. et al. Inflammation and DNA damage: cause, effect or both. Nat. Rev. Rheumatol. 19, 200–211 (2023).
pubmed: 36750681
doi: 10.1038/s41584-022-00905-1
Kawanishi, S., Ohnishi, S., Ma, N., Hiraku, Y. & Murata, M. Crosstalk between DNA damage and inflammation in the multiple steps of carcinogenesis. Int. J. Mol. Sci. 18 (2017).
Kay, J., Thadhani, E., Samson, L. & Engelward, B. Inflammation-induced DNA damage, mutations and cancer. DNA Repair. 83, 102673 (2019).
pubmed: 31387777
pmcid: 6801086
doi: 10.1016/j.dnarep.2019.102673
Igusa, T. et al. Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer. Ann. Rheum. Dis. 77, 1179–1186 (2018).
pubmed: 29678941
Usategui, A. et al. Evidence of telomere attrition and a potential role for DNA damage in systemic sclerosis. Immun. Ageing 19, 7 (2022).
pubmed: 35086525
pmcid: 8793167
doi: 10.1186/s12979-022-00263-2
Vlachogiannis, N. I. et al. Association between DNA damage response, fibrosis and Type I Interferon signature in systemic sclerosis. Front. Immunol. 11, 582401 (2020).
pubmed: 33123169
pmcid: 7566292
doi: 10.3389/fimmu.2020.582401
Paul, S. et al. Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis. Nat. Commun. 13, 7074 (2022).
pubmed: 36400785
pmcid: 9674829
doi: 10.1038/s41467-022-34775-8
Gniadecki, R. et al. Genomic instability in early systemic sclerosis. J. Autoimmun. 131, 102847 (2022).
pubmed: 35803104
doi: 10.1016/j.jaut.2022.102847
Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122–128 (2020).
pubmed: 32025013
pmcid: 7054212
doi: 10.1038/s41586-019-1907-7
Kendall, R. T. & Feghali-Bostwick, C. A. Fibroblasts in fibrosis: novel roles and mediators. Front. Pharm. 5, 123 (2014).
doi: 10.3389/fphar.2014.00123
Huang, L., Ma, F., Chapman, A., Lu, S. & Xie, X. S. Single-cell whole-genome amplification and sequencing: methodology and applications. Annu. Rev. Genomics Hum. Genet. 16, 79–102 (2015).
pubmed: 26077818
doi: 10.1146/annurev-genom-090413-025352
Dong, X. et al. Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat. Methods 14, 491–493 (2017).
pubmed: 28319112
pmcid: 5408311
doi: 10.1038/nmeth.4227
Saini, N. et al. UV-exposure, endogenous DNA damage, and DNA replication errors shape the spectra of genome changes in human skin. PLoS Genet. 17, e1009302 (2021).
pubmed: 33444353
pmcid: 7808690
doi: 10.1371/journal.pgen.1009302
Shinbrot, E. et al. Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication. Genome Res. 24, 1740–1750 (2014).
pubmed: 25228659
pmcid: 4216916
doi: 10.1101/gr.174789.114
Lujan, S. A. et al. Mismatch repair balances leading and lagging strand DNA replication fidelity. PLoS Genet. 8, e1003016 (2012).
pubmed: 23071460
pmcid: 3469411
doi: 10.1371/journal.pgen.1003016
Haradhvala, N. J. et al. Mutational strand asymmetries in cancer genomes reveal mechanisms of DNA damage and repair. Cell 164, 538–549 (2016).
pubmed: 26806129
pmcid: 4753048
doi: 10.1016/j.cell.2015.12.050
Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
pubmed: 23945592
pmcid: 3776390
doi: 10.1038/nature12477
Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020).
pubmed: 32025018
pmcid: 7054213
doi: 10.1038/s41586-020-1943-3
Senkin, S. MSA: reproducible mutational signature attribution with confidence based on simulations. BMC Bioinforma. 22, 540 (2021).
doi: 10.1186/s12859-021-04450-8
Deneuve, S. et al. Molecular landscapes of oral cancers of unknown etiology. medRxiv (2023).
Wu, A. J., Perera, A., Kularatnarajah, L., Korsakova, A. & Pitt, J. J. Mutational signature assignment heterogeneity is widespread and can be addressed by ensemble approaches. Brief Bioinform. 24 (2023).
Huang, X., Wojtowicz, D. & Przytycka, T. M. Detecting presence of mutational signatures in cancer with confidence. Bioinformatics 34, 330–337 (2018).
pubmed: 29028923
doi: 10.1093/bioinformatics/btx604
Koh, G., Degasperi, A., Zou, X., Momen, S. & Nik-Zainal, S. Mutational signatures: emerging concepts, caveats and clinical applications. Nat. Rev. Cancer 21, 619–637 (2021).
pubmed: 34316057
doi: 10.1038/s41568-021-00377-7
Petljak, M. et al. Characterizing mutational signatures in human cancer cell lines reveals episodic APOBEC Mutagenesis. Cell 176, 1282–1294.e20 (2019).
pubmed: 30849372
pmcid: 6424819
doi: 10.1016/j.cell.2019.02.012
Rouhani, F. J. et al. Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells. PLoS Genet 12, e1005932 (2016).
pubmed: 27054363
pmcid: 4824386
doi: 10.1371/journal.pgen.1005932
Kuijk, E. et al. The mutational impact of culturing human pluripotent and adult stem cells. Nat. Commun. 11, 2493 (2020).
pubmed: 32427826
pmcid: 7237696
doi: 10.1038/s41467-020-16323-4
Milholland, B. et al. Differences between germline and somatic mutation rates in humans and mice. Nat. Commun. 8, 15183 (2017).
pubmed: 28485371
pmcid: 5436103
doi: 10.1038/ncomms15183
Vijayraghavan, S., Porcher, L., Mieczkowski, P. A. & Saini, N. Acetaldehyde makes a distinct mutation signature in single-stranded DNA. Nucleic Acids Res. 50, 7451–7464 (2022).
pubmed: 35776120
pmcid: 9303387
doi: 10.1093/nar/gkac570
Roberts, S. A. et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat. Genet 45, 970–976 (2013).
pubmed: 23852170
pmcid: 3789062
doi: 10.1038/ng.2702
Pham, P., Bransteitter, R., Petruska, J. & Goodman, M. F. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424, 103–107 (2003).
pubmed: 12819663
doi: 10.1038/nature01760
Rogozin, I. B. et al. Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers. Sci. Rep. 6, 38133 (2016).
pubmed: 27924834
pmcid: 5141443
doi: 10.1038/srep38133
Bergstrom, E. N. et al. SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events. BMC Genomics 20, 685 (2019).
pubmed: 31470794
pmcid: 6717374
doi: 10.1186/s12864-019-6041-2
Matsuda, T., Kawanishi, M., Yagi, T., Matsui, S. & Takebe, H. Specific tandem GG to TT base substitutions induced by acetaldehyde are due to intra-strand crosslinks between adjacent guanine bases. Nucleic Acids Res. 26, 1769–1774 (1998).
pubmed: 9512551
pmcid: 147446
doi: 10.1093/nar/26.7.1769
Sonohara, Y. et al. Acetaldehyde forms covalent GG intrastrand crosslinks in DNA. Sci. Rep. 9, 660 (2019).
pubmed: 30679737
pmcid: 6345987
doi: 10.1038/s41598-018-37239-6
Otlu, B. et al. Topography of mutational signatures in human cancer. Cell Rep. 42, 112930 (2023).
pubmed: 37540596
pmcid: 10507738
doi: 10.1016/j.celrep.2023.112930
Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979–993 (2012).
pubmed: 22608084
pmcid: 3414841
doi: 10.1016/j.cell.2012.04.024
Roberts, S. A. et al. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol. Cell 46, 424–435 (2012).
pubmed: 22607975
pmcid: 3361558
doi: 10.1016/j.molcel.2012.03.030
Bergstrom, E. N., Kundu, M., Tbeileh, N. & Alexandrov, L. B. Examining clustered somatic mutations with SigProfilerClusters. Bioinformatics 38, 3470–3473 (2022).
pubmed: 35595234
pmcid: 9237733
doi: 10.1093/bioinformatics/btac335
Wang, Y. et al. APOBEC mutagenesis is a common process in normal human small intestine. Nat. Genet 55, 246–254 (2023).
pubmed: 36702998
pmcid: 9925384
doi: 10.1038/s41588-022-01296-5
Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).
pubmed: 22300766
pmcid: 3290792
doi: 10.1101/gr.129684.111
Wala, J. A. et al. SvABA: genome-wide detection of structural variants and indels by local assembly. Genome Res. 28, 581–591 (2018).
pubmed: 29535149
pmcid: 5880247
doi: 10.1101/gr.221028.117
Rausch, T. et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics 28, i333–i339 (2012).
pubmed: 22962449
pmcid: 3436805
doi: 10.1093/bioinformatics/bts378
MacDonald, J. R., Ziman, R., Yuen, R. K., Feuk, L. & Scherer, S. W. The database of genomic variants: a curated collection of structural variation in the human genome. Nucleic Acids Res. 42, D986–D992 (2014).
pubmed: 24174537
doi: 10.1093/nar/gkt958
Fickelscher, I. et al. The variant inv(2)(p11.2q13) is a genuinely recurrent rearrangement but displays some breakpoint heterogeneity. Am. J. Hum. Genet 81, 847–856 (2007).
pubmed: 17847011
pmcid: 2227935
doi: 10.1086/521226
Tamborero, D. et al. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations. Genome Med. 10, 25 (2018).
pubmed: 29592813
pmcid: 5875005
doi: 10.1186/s13073-018-0531-8
Olafsson, S. et al. Somatic Evolution in Non-neoplastic IBD-Affected Colon. Cell 182, 672–684.e11 (2020).
pubmed: 32697969
pmcid: 7427325
doi: 10.1016/j.cell.2020.06.036
Rogozin, I. B. et al. DNA polymerase eta mutational signatures are found in a variety of different types of cancer. Cell Cycle 17, 348–355 (2018).
pubmed: 29139326
pmcid: 5914734
doi: 10.1080/15384101.2017.1404208
Nada, S., Kahaleh, B. & Altorok, N. Genome-wide DNA methylation pattern in systemic sclerosis microvascular endothelial cells: Identification of epigenetically affected key genes and pathways. J. Scleroderma Relat. Disord. 7, 71–81 (2022).
pubmed: 35386944
doi: 10.1177/23971983211033772
Folmsbee, S. S., Budinger, G. R. S., Bryce, P. J. & Gottardi, C. J. The cardiomyocyte protein alphaT-catenin contributes to asthma through regulating pulmonary vein inflammation. J. Allergy Clin. Immunol. 138, 123–129.e2 (2016).
pubmed: 26947180
pmcid: 4931945
doi: 10.1016/j.jaci.2015.11.037
Islam, S. M. A. et al. Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor. Cell Genom. 2 (2022).
Burgers, P. M. et al. Eukaryotic DNA polymerases: proposal for a revised nomenclature. J. Biol. Chem. 276, 43487–43490 (2001).
pubmed: 11579108
doi: 10.1074/jbc.R100056200
McCulloch, S. D. & Kunkel, T. A. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 18, 148–161 (2008).
pubmed: 18166979
doi: 10.1038/cr.2008.4
Washington, M. T., Johnson, R. E., Prakash, L. & Prakash, S. Accuracy of lesion bypass by yeast and human DNA polymerase eta. Proc. Natl Acad. Sci. USA 98, 8355–8360 (2001).
pubmed: 11459975
pmcid: 37443
doi: 10.1073/pnas.121007298
Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F. & Kunkel, T. A. Low fidelity DNA synthesis by human DNA polymerase-eta. Nature 404, 1011–1013 (2000).
pubmed: 10801132
doi: 10.1038/35010014
Saini, N. et al. The impact of environmental and endogenous damage on somatic mutation load in human skin fibroblasts. PLoS Genet. 12, e1006385 (2016).
pubmed: 27788131
pmcid: 5082821
doi: 10.1371/journal.pgen.1006385
Matsuda, T. et al. Error rate and specificity of human and murine DNA polymerase eta. J. Mol. Biol. 312, 335–346 (2001).
pubmed: 11554790
doi: 10.1006/jmbi.2001.4937
Rogozin, I. B. et al. Mutational signatures and mutable motifs in cancer genomes. Brief. Bioinform. 19, 1085–1101 (2018).
pubmed: 28498882
Martincorena, I. et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880–886 (2015).
pubmed: 25999502
pmcid: 4471149
doi: 10.1126/science.aaa6806
Yoshida, K. et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 578, 266–272 (2020).
pubmed: 31996850
pmcid: 7021511
doi: 10.1038/s41586-020-1961-1
Kiraly, O., Gong, G., Olipitz, W., Muthupalani, S. & Engelward, B. P. Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet. 11, e1004901 (2015).
pubmed: 25647331
pmcid: 4372043
doi: 10.1371/journal.pgen.1004901
Muramatsu, M. et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J. Biol. Chem. 274, 18470–18476 (1999).
pubmed: 10373455
doi: 10.1074/jbc.274.26.18470
Mao, C. et al. T cell-independent somatic hypermutation in murine B cells with an immature phenotype. Immunity 20, 133–144 (2004).
pubmed: 14975236
doi: 10.1016/S1074-7613(04)00019-6
William, J., Euler, C., Christensen, S. & Shlomchik, M. J. Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297, 2066–2070 (2002).
pubmed: 12242446
doi: 10.1126/science.1073924
Schroder, A. E., Greiner, A., Seyfert, C. & Berek, C. Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc. Natl Acad. Sci. USA 93, 221–225 (1996).
pubmed: 8552609
pmcid: 40210
doi: 10.1073/pnas.93.1.221
Okazaki, I. M. et al. Constitutive expression of AID leads to tumorigenesis. J. Exp. Med. 197, 1173–1181 (2003).
pubmed: 12732658
pmcid: 2193972
doi: 10.1084/jem.20030275
Casellas, R. et al. Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity. Nat. Rev. Immunol. 16, 164–176 (2016).
pubmed: 26898111
pmcid: 4871114
doi: 10.1038/nri.2016.2
Li, L. et al. Activation-induced cytidine deaminase expression in colorectal cancer. Int J. Clin. Exp. Pathol. 12, 4119–4124 (2019).
pubmed: 31933808
pmcid: 6949800
Nonaka, T. et al. Involvement of activation-induced cytidine deaminase in skin cancer development. J. Clin. Invest. 126, 1367–1382 (2016).
pubmed: 26974156
pmcid: 4811119
doi: 10.1172/JCI81522
Sawai, Y. et al. Activation-induced cytidine deaminase contributes to pancreatic tumorigenesis by inducing tumor-related gene mutations. Cancer Res. 75, 3292–3301 (2015).
pubmed: 26113087
doi: 10.1158/0008-5472.CAN-14-3028
Taylor, B. J. et al. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife 2, e00534 (2013).
pubmed: 23599896
pmcid: 3628087
doi: 10.7554/eLife.00534
Abyzov, A. et al. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492, 438–442 (2012).
pubmed: 23160490
pmcid: 3532053
doi: 10.1038/nature11629
Zhou, Y. et al. Single-cell multiomics sequencing reveals prevalent genomic alterations in tumor stromal cells of human colorectal cancer. Cancer Cell 38, 818–828.e5 (2020).
pubmed: 33096021
doi: 10.1016/j.ccell.2020.09.015
Hsu, E. et al. Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension. Arthritis Rheum. 63, 783–794 (2011).
pubmed: 21360508
pmcid: 3139818
doi: 10.1002/art.30159
Renaud, L., da Silveira, W. A., Takamura, N., Hardiman, G. & Feghali-Bostwick, C. Prominence of IL6, IGF, TLR, and bioenergetics pathway perturbation in lung tissues of scleroderma patients with pulmonary fibrosis. Front. Immunol. 11, 383 (2020).
pubmed: 32210969
pmcid: 7075854
doi: 10.3389/fimmu.2020.00383
Pedersen, B. S., Collins, R. L., Talkowski, M. E. & Quinlan, A. R. Indexcov: fast coverage quality control for whole-genome sequencing. Gigascience 6, 1–6 (2017).
pubmed: 29048539
pmcid: 5737511
doi: 10.1093/gigascience/gix090
Koboldt, D. C. Best practices for variant calling in clinical sequencing. Genome Med. 12, 91 (2020).
pubmed: 33106175
pmcid: 7586657
doi: 10.1186/s13073-020-00791-w
Saunders, C. T. et al. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28, 1811–1817 (2012).
pubmed: 22581179
doi: 10.1093/bioinformatics/bts271
Larson, D. E. et al. SomaticSniper: identification of somatic point mutations in whole genome sequencing data. Bioinformatics 28, 311–317 (2012).
pubmed: 22155872
doi: 10.1093/bioinformatics/btr665
Gel, B. & Serra, E. karyoploteR: an R/Bioconductor package to plot customizable genomes displaying arbitrary data. Bioinformatics 33, 3088–3090 (2017).
pubmed: 28575171
pmcid: 5870550
doi: 10.1093/bioinformatics/btx346
Blokzijl, F., Janssen, R., van Boxtel, R. & Cuppen, E. MutationalPatterns: comprehensive genome-wide analysis of mutational processes. Genome Med. 10, 33 (2018).
pubmed: 29695279
pmcid: 5922316
doi: 10.1186/s13073-018-0539-0
Zhang, H., Meltzer, P. & Davis, S. RCircos: an R package for Circos 2D track plots. BMC Bioinforma. 14, 244 (2013).
doi: 10.1186/1471-2105-14-244