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An Integrative Anal...
An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas
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- Miyashita, Naoya (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan,University of Tokyo
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- Horie, Masafumi (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan;Univ Southern Calif, Hastings Ctr Pulm Res, Div Pulm Crit Care & Sleep Med, Dept Med,Keck Sch Med, Los Angeles, CA USA;RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa, Japan,RIKEN Nishina Center for Accelerator-Based Science,University of Southern California,University of Tokyo
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- Suzuki, Hiroshi I. (författare)
- MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA,Massachusetts Institute of Technology
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- Yoshihara, Masahito (författare)
- RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa, Japan,RIKEN Nishina Center for Accelerator-Based Science
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- Djureinovic, Dijana (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Fredrik Pontén
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- Persson, Johan (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Brunnström, Hans (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Lindskog, Cecilia (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
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- Elfving, Hedvig (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Micke, Patrick (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Saito, Akira (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan;Univ Tokyo, Div Hlth Serv Promot, Tokyo, Japan,University of Tokyo
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- Nagase, Takahide (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan,University of Tokyo
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(creator_code:org_t)
- ELSEVIER SCIENCE INC, 2018
- 2018
- Engelska.
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 13:11, s. 1676-1691
- Relaterad länk:
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http://www.jto.org/a...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete-scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung cancer and large cell neuroendocrine carcinoma. Methods: The aim of this study was to characterize clinical and molecular features of ASCL1-positive lung adenocarcinoma by using recent transcriptome profiling in multiple patient cohorts and genome-wide epigenetic profiling including data from The Cancer Genome Atlas. Results: The ASCL1-positive subtype of lung adenocarcinoma developed preferentially in current or former smokers and usually did not harbor EGFR mutations. In transcriptome profiling, this subtype overlapped with the recently proposed proximal-proliferative molecular subtype. Gene expression profiling of ASCL1-positive cases suggested generally poor immune cell infiltration and none of the tumors were positive for programmed cell death ligand 1 protein expression. Genome-wide methylation analysis showed global DNA hypomethylation in ASCL1-positive cases. ASCL1 was associated with super-enhancers in ASCL1-positive lung adenocarcinoma cells, and ASCL1 silencing suppressed other super-enhancer-associated genes, suggesting thatASCL1 acts as a master transcriptional regulator. This was further reinforced by the essential roles of ASCL1 in cell proliferation, survival, and cell cycle control. Conclusions: These results suggest that ASCL1 defines a subgroup of lung adenocarcinoma with distinct molecular features by driving super-enhancer-mediated transcriptional programs.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Nyckelord
- Lung cancer
- Adenocarcinoma
- Neuroendocrine
- ASCL1
- NSCLC
- Patologi
- Pathology
- Adenocarcinoma
- ASCL1
- Lung cancer
- Neuroendocrine
- NSCLC
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Miyashita, Naoya
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Horie, Masafumi
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Suzuki, Hiroshi ...
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Yoshihara, Masah ...
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Djureinovic, Dij ...
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Persson, Johan
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Brunnström, Hans
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Lindskog, Cecili ...
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Elfving, Hedvig
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Micke, Patrick
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Saito, Akira
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Nagase, Takahide
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Uppsala universitet
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Lunds universitet