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Somatic PRDM2 c.446...
Somatic PRDM2 c.4467delA mutations in colorectal cancers control histone methylation and tumor growth
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- Pandzic, Tatjana (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Rendo, Verónica (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Lim, Jinyeong (author)
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyangsi, Republic of Korea
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- Larsson, Chatarina, 1979- (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Larsson, Jimmy, 1977- (author)
- Uppsala universitet,Molekylär systembiologi,Science for Life Laboratory, SciLifeLab
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- Stoimenov, Ivaylo (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Kundu, Snehangshu (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Ali, Muhammad Akhtar (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi
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- Hellström, Mats (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Lindroth, Anders M. (author)
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyangsi, Republic of Korea
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- Sjöblom, Tobias (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2017-10-09
- 2017
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:58, s. 98646-98659
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https://doi.org/10.1...
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Abstract
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- The chromatin modifier PRDM2/RIZ1 is inactivated by mutation in several forms of cancer and is a putative tumor suppressor gene. Frameshift mutations in the C-terminal region of PRDM2, affecting (A)8 or (A)9 repeats within exon 8, are found in one third of colorectal cancers with microsatellite instability, but the contribution of these mutations to colorectal tumorigenesis is unknown. To model somatic mutations in microsatellite unstable tumors, we devised a general approach to perform genome editing while stabilizing the mutated nucleotide repeat. We then engineered isogenic cell systems where the PRDM2 c.4467delA mutation in human HCT116 colorectal cancer cells was corrected to wild-type by genome editing. Restored PRDM2 increased global histone 3 lysine 9 dimethylation and reduced migration, anchorage-independent growth and tumor growth in vivo. Gene set enrichment analysis revealed regulation of several hallmark cancer pathways, particularly of epithelial-to-mesenchymal transition (EMT), with VIM being the most significantly regulated gene. These observations provide direct evidence that PRDM2 c.4467delA is a driver mutation in colorectal cancer and confirms PRDM2 as a cancer gene, pointing to regulation of EMT as a central aspect of its tumor suppressive action.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Oncotarget
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- By the author/editor
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Pandzic, Tatjana
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Rendo, Verónica
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Lim, Jinyeong
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Larsson, Chatari ...
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Larsson, Jimmy, ...
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Stoimenov, Ivayl ...
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show more...
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Kundu, Snehangsh ...
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Ali, Muhammad Ak ...
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Hellström, Mats
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He, Liqun
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Lindroth, Anders ...
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Sjöblom, Tobias
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Oncotarget
- By the university
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Uppsala University