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CUL3 and NRF2 Mutations Confer an NRF2 Activation Phenotype in a Sporadic Form of Papillary Renal Cell Carcinoma
Published version of a preprint
Abstract
Sustained activation of the stress-regulated transcription factor NRF2 (NFE2L2) is a prominent feature of many types of cancer, implying that mutations driving NRF2 may be important to tumor progression. In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2. Here we show that somatic mutations in NRF2, CUL3, and SIRT1 are responsible for driving the NRF2 activation phenotype in sporadic PRCC2. Transcriptome sequencing revealed the expression pattern of mutant alleles of NRF2, CUL3, and SIRT1 and also confirmed NRF2 activation in clinical specimens. Our results show a convergence in somatic mutations in sporadic PRCC2 with FH mutation in hereditary PRCC2. Cancer Res; 73(7); 2044–51. ©2013 AACR.
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“Some somatic mutations give rise to hyperactive Nrf2, which causes enhanced antioxidant capacity and confers protection of cancer cells from ROS and cancer therapy, thereby leading to cancer cell growth and proliferation, cancer progression, and cancer therapy resistance (e.g., chemoresistance) (Figure 8) [161,162,163,164,165,166,167,168,169,170,171].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [166]
In the citing paper
“most of which have been attributed to loss-of-function mutations in the KEAP1 gene and/or gain-of-function mutations in the NFE2L2 gene encoding Nrf2 [162,163,164,166,167].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [166]
Citations
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
The variant call format and VCFtools
Danecek, P., Auton, A., Abecasis, G. R., Albers, C. A., Banks, E., DePristo, M. A., Handsaker, R. E., Lunter, G. A., Marth, G., Sherry, S. T., et al. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr330 · Cited by 16,450
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
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Ong, A. J. S., Saeidi, S., Kieu, N. H., Kim, S. J., Kim, D., Kim, S. H., Park, S., Cha, Y., Na, H., & Surh, Y. (2020) · Free Radical Research · doi:10.1080/10715762.2020.1761547 · Cited by 15
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Guan, L., Torres‐Saavedra, P. A., Zhao, X., Major, M. B., Holmes, B., Nguyen, N. K., Kumaravelu, P., Hodge, T., Diehn, M., Zevallos, J. P., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-2334 · Cited by 11
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Gummlich, L., Kähne, T., Naumann, M., Kilic, E., Jung, K., & Dubiel, W. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2015.12.007 · Cited by 6
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Huang, P., Wang, S., Wu, Z., Zhou, Z., Kuang, M., Ren, C., Qian, X., Jiang, A., Zhou, Y., Wang, X., et al. (2022) · Medicine · doi:10.1097/md.0000000000030222 · Cited by 2
Park, J. H., Shin, S., Kim, H. J., Oh, S., & Cho, Y. M. (2024) · Journal of Pathology and Translational Medicine · doi:10.4132/jptm.2024.07.31 · Cited by 2
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Oosterwijk, E., & Mulders, P. (2020) · Springer eBooks · doi:10.1007/978-3-030-28599-9_33 · Cited by 1
Ozcan, A., Krishnan, B., & Truong, L. D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-386456-7.05415-0 · Cited by 1
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Ibeawuchi, S., Quelle, F. W., Fisher, R. A., Faraci, F. M., Miller, F. J., & Sigmund, C. D. (2015) · doi:10.17077/etd.7mrtj5hl · Cited by 1
The physiological, pharmacological and toxicological roles of Nrf2 in the kidney
Shelton, L. M. (2015) · University of Liverpool · doi:10.17638/02014505
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Kwan, S. Y. (2015) · Digital Commons-TMC (Texas Medical Center)
Su, D., Metwalli, A. R., & Srinivasan, R. (2016) · Springer eBooks · doi:10.1007/978-3-319-30046-7_1
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Harder, B. G. (2017) · UA Campus Repository (The University of Arizona)
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Arun, K. B., Varghese, M. V., & Ayyappan, P. (2021) · Springer eBooks · doi:10.1007/978-981-15-4501-6_66-1
Yildiz, M., & Seğmen, H. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.102753
Insights into the Role of NRf2 Pathway in Cadmium-Induced Carcinogenesis
Arun, K. B., Varghese, M. V., & Ayyappan, P. (2022) · Springer eBooks · doi:10.1007/978-981-15-9411-3_66
Nadai, C., Novakovic, A., Pal, S. K., & Figlin, R. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-47871-7.00049-6
Liu, N., Shen, C., Zhou, T., Zhou, Y., Yuan, H., Bi, H., Wang, Y., Pei, X., Su, R. J., Trisal, V., et al. (2026) · Cancer & Metabolism · doi:10.1186/s40170-026-00435-4 · Cited by 1
Fengzhi, L. I., Aljahdali, I. A. M., Zhang, R., Nastiuk, K. L., Krolewski, J. J., & Ling, X. (2021) · Figshare · doi:10.6084/m9.figshare.15162096
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de Bourayne, M. (2015) · theses.fr (ABES) · doi:10.70675/fed3e8c8z64c2z4e1ez81a9z054e2d240b5f
Metadata
- Authors
- Ooi, A., Dykema, K., Ansari, A., Petillo, D., Snider, J., Kahnoski, R., Anema, J., Craig, D., Carpten, J., Teh, B.-T., & Furge, K. A.
- Affiliations
- Van Andel Institute (US)
- Venue
- Cancer Research
- Published
- 2013-04-01
- Volume
- 73
- Issue
- 7
- Pages
- 2044-2051
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2135514225
- Cited by
- 159
- References
- 35
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 13 · 2021: 9 · 2020: 19 · 2019: 17 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 20 · 2014: 13 · 2013: 8
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- papillary renal cell carcinoma, Nrf2 activation, CUL3, NRF2 mutation, SIRT1, fumarate hydratase, hereditary leiomyomatosis and renal cell carcinoma, somatic mutations, fumarate accumulation, tumor progression
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Amino Acid Sequence, Carcinoma, Renal Cell, Cells, Cultured, Humans, Immunoenzyme Techniques, Kidney Neoplasms, Kidney Tubules, Proximal, Molecular Sequence Data, Mutation, Phenotype, Biomarkers, Tumor, Blotting, Western, Sequence Homology, Amino Acid, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cullin Proteins, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2, Sirtuin 1, High-Throughput Nucleotide Sequencing
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