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Deficiency of nucleotide excision repair is associated with mutational signature observed in cancer
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Abstract
Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Disruption of this pathway can contribute to the development of cancer and accelerate aging. Mutational characteristics of NER-deficiency may reveal important diagnostic opportunities, as tumors deficient in NER are more sensitive to certain treatments. Here, we analyzed the genome-wide somatic mutational profiles of adult stem cells (ASCs) from NER-deficient Ercc1 −/Δ mice. Our results indicate that NER-deficiency increases the base substitution load twofold in liver but not in small intestinal ASCs, which coincides with the tissue-specific aging pathology observed in these mice. Moreover, NER-deficient ASCs of both tissues show an increased contribution of Signature 8 mutations, which is a mutational pattern with unknown etiology that is recurrently observed in various cancer types. The scattered genomic distribution of the base substitutions indicates that deficiency of global-genome NER (GG-NER) underlies the observed mutational consequences. In line with this, we observe increased Signature 8 mutations in a GG-NER-deficient human organoid culture, in which XPC was deleted using CRISPR-Cas9 gene-editing. Furthermore, genomes of NER-deficient breast tumors show an increased contribution of Signature 8 mutations compared with NER-proficient tumors. Elevated levels of Signature 8 mutations could therefore contribute to a predictor of NER-deficiency based on a patient's mutational profile.
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Far less is known about somatic mutation in other species than in humans.
“With the exception of some initial studies, far less is known about somatic mutation in other species1–7.”
From Somatic mutation rates scale with lifespan across mammals (2022) · cites this paper as [5]
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Van der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · cited 2×
“The livers of Ercc1 − / Δ mice display various aging-like characteristics (Weeda et al. 1997; Niedernhofer et al. 2006; Dollé et al. 2011; Gregg et al. 2012), whereas other organs do not show an obvious pathological phenotype.”
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218
A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619
Self-citationUnderstanding nucleotide excision repair and its roles in cancer and ageing
Marteijn, J. A., Lans, H., Vermeulen, W., & Hoeijmakers, J. H. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3822 · Cited by 1,192
Self-citationTissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935
Self-citationDNA repair mechanisms in dividing and non-dividing cells
Iyama, T., & Wilson, D. M. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.04.015 · Cited by 697
MutationalPatterns: comprehensive genome-wide analysis of mutational processes
Blokzijl, F., Janssen, R., van Boxtel, R., & Cuppen, E. (2018) · Genome Medicine · doi:10.1186/s13073-018-0539-0 · Cited by 660
Self-citationChromatin organization is a major influence on regional mutation rates in human cancer cells
Schuster-Böckler, B., & Lehner, B. (2012) · Nature · doi:10.1038/nature11273 · Cited by 657 · cited 2×
“Mutations are distributed non-randomly throughout the genome in cancer cells and in human ASCs (Schuster-Böckler and Lehner 2012; Blokzijletal.2016).”
Aging and neurodegeneration are associated with increased mutations in single human neurons
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., et al. (2018) · Science · doi:10.1126/science.aao4426 · Cited by 635
Therapeutic opportunities within the DNA damage response
Pearl, L. H., Schierz, A. C., Ward, S. E., Al-Lazikani, B., & Pearl, F. M. G. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3891 · Cited by 587
Drost, J., van Boxtel, R., Blokzijl, F., Mizutani, T., Sasaki, N., Sasselli, V., de Ligt, J., Behjati, S., Grolleman, J. E., van Wezel, T., et al. (2017) · Science · doi:10.1126/science.aao3130 · Cited by 461
Self-citationRestricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice
Vermeij, W. P., Dollé, M. E. T., Reiling, E., Jaarsma, D., Payan-Gomez, C., Bombardieri, C. R., Wu, H., Roks, A. J. M., Botter, S. M., van der Eerden, B. C., et al. (2016) · Nature · doi:10.1038/nature19329 · Cited by 315
Self-citationOxidatively generated complex DNA damage: Tandem and clustered lesions
Cadet, J., Ravanat, J.-L., TavernaPorro, M., Menoni, H., & Angelov, D. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.04.005 · Cited by 233
Broad segmental progeroid changes in short-lived Ercc1 −/Δ7 mice
Dollé, M. E. T., Kuiper, R. V., Roodbergen, M., Robinson, J., de Vlugt, S., Wijnhoven, S. W. P., Beems, R. B., de la Fonteyne, L., de With, P., van der Pluijm, I., et al. (2011) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v1i0.7219 · Cited by 91
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Flagged first, then by citations
Research works printed but not linked: 46
- 10.1016/0092-8674(95)90289-9 · DOI · Paper page
- 10.1016/j.stem.2015.05.002 · DOI
- 10.1038/nature12477 · DOI · Paper page
- 10.1038/ng.3441 · DOI
- 10.1101/322859 · DOI
- 10.1093/nar/gkm888 · DOI
- 10.1186/gb-2010-11-10-r106 · DOI · Paper page
- 10.1038/nature07602 · DOI
- 10.1038/nature13448 · DOI · Paper page
- 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page
- 10.1073/pnas.1000193107 · DOI
- 10.1093/bioinformatics/btr670 · DOI
- 10.1038/sj.leu.2404376 · DOI
- 10.1038/nm.4292 · DOI · Paper page
- 10.1093/nar/gkt671 · DOI
- 10.1093/nar/26.18.4146 · DOI
- 10.1016/j.mrfmmm.2005.11.008 · DOI
- 10.1016/j.mrfmmm.2014.08.007 · DOI
- 10.1093/bioinformatics/bti525 · DOI
- 10.1038/nprot.2009.97 · DOI
- 10.1002/hep.24713 · DOI
- 10.1056/NEJMra0804615 · DOI · Paper page
- 10.1101/gr.220038.116 · DOI
- 10.1093/carcin/16.4.883 · DOI
- 10.1038/ng.3557 · DOI
- 2010, Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs, Anticancer Res, 30, 3223
- 10.1038/srep22154 · DOI
- 10.1093/nar/gkf478 · DOI
- 10.1158/0008-5472.CAN-07-6067 · DOI
- 10.1038/srep04112 · DOI
- 10.1038/nature05456 · DOI · Paper page
- 10.1038/nature17437 · DOI
- 10.1007/s00018-015-2075-z · DOI
- 10.1002/em.20583 · DOI
- 10.1093/bioinformatics/bts378 · DOI
- 10.1038/nbt.1754 · DOI · Paper page
- 10.1038/377162a0 · DOI
- 10.1038/nature07935 · DOI · Paper page
- 10.1016/S0092-8674(00)80155-5 · DOI
- 10.1093/nar/24.17.3370 · DOI
- 10.1074/jbc.M111.337899 · DOI
- 10.1016/j.str.2005.08.014 · DOI
- 10.1016/S0960-9822(06)00190-4 · DOI
- 10.1016/j.celrep.2014.10.031 · DOI
- 10.1016/j.cell.2016.07.045 · DOI
- 10.1038/s41467-018-04052-8 · DOI
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Somatic genomic changes in single Alzheimer’s disease neurons
Miller, M. B., Huang, A. Y., Kim, J., Zhou, Z., Kirkham, S. L., Maury, E. A., Ziegenfuss, J. S., Reed, H. C., Neil, J. E., Rento, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04640-1 · Cited by 223
Portrait of a cancer: mutational signature analyses for cancer diagnostics
Van Hoeck, A., Tjoonk, N. H., van Boxtel, R., & Cuppen, E. (2019) · BMC Cancer · doi:10.1186/s12885-019-5677-2 · Cited by 107
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Wu, C.-C., & Livingston, J. A. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-43085-6_2 · Cited by 58
Ren, P., Zheng, C., Pang, Y., Qiang, Y., Sun, S., Wang, Q., Xu, W., Lee, M., Lu, Z., Zhou, M., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-01011-z · Cited by 6
Metadata
- Authors
- Jager, M., Blokzijl, F., Kuijk, E., Bertl, J., Vougioukalaki, M., Janssen, R., Besselink, N., Boymans, S., de Ligt, J., Pedersen, J. S., Hoeijmakers, J., Pothof, J., van Boxtel, R., & Cuppen, E.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2019-06-20
- Volume
- 29
- Issue
- 7
- Pages
- 1067-1077
- ISSN
- 1088-9051
- 1549-5469
- PMC
- PMC6633256
- Cited by
- 98
- References
- 16
- Language
- en
- Funders
- Netherlands Organisation for Scientific Research (016.Vidi.171.023)
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