Evidence map›Paper›PMID 37591951›Full record

ArticleNature cell biology2023

KDM6A epigenetically regulates subtype plasticity in small cell lung cancer.

Leslie Duplaquet, Yixiang Li, Matthew A Booker, Yingtian Xie, Sarah Naomi Olsen, Radhika A Patel, Deli Hong, Charlie Hatton, Thomas Denize, Emily Walton and 14 more

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Review
  3. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
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  14. Article
  15. Article
  16. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 1 country.

Leslie Duplaquet *Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6544-0432
Yixiang Li *Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Matthew A BookerDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, USA.
Yingtian XieDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sarah Naomi OlsenDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9136-0778
Radhika A PatelDivision of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Deli HongDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Charlie HattonDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9903-4291
Thomas DenizeDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Emily WaltonDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2117-5988
Yasmin N LaimonDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0848-9843
Rong LiDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0000-1046-9580
Yijia JiangDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Roderick T BronsonDivision of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Jackson SouthardTranslational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.
Shuqiang LiTranslational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9106-6141
Sabina SignorettiDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5000-9105
Xintao QiuDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8560-7017
Paloma CejasDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2090-7748
Scott A ArmstrongDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9099-4728
Henry W LongDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
Michael Y TolstorukovDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, USA.
Michael C HaffnerDivision of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Matthew G OserDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Matthew_Oser@dfci.harvard.edu.ORCID http://orcid.org/0000-0003-2047-0969
Brigham and Women's Hospital · USDana-Farber Cancer Institute · USBoston Children's Hospital · USBroad Institute · USFred Hutch Cancer Center · USHarvard University · USUniversity of Washington · US

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Targeting to Epigenetic Modications in ALLR01CA176745 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ARMSTRONG, SCOTT A, QI, JUN · 2012 to 2022
$4.2M
Defining epigenetic mechanisms in NPM1c mutant leukemiaR01CA259273 · NCI · DANA-FARBER CANCER INST · PI ARMSTRONG, SCOTT A · 2021 to 2025
$2.0M
Mechanisms by which LSD1 Promotes Neuroendocrine Differentiation and Small Cell Lung CancerR37CA269990 · NCI · DANA-FARBER CANCER INST · PI Matthew Gilbert Oser · 2023 to 2026
$1.8M
Single cell investigation of co-evolution in cancer cells and host cell immune microenvironmentR50CA251956 · NCI · DANA-FARBER CANCER INST · PI Shuqiang Li · 2020 to 2026
$1.4M
New Therapeutic Targets in Small Cell Lung Cancer that are Epistatic or Synthetic Lethal with pRB LossK08CA222657 · NCI · DANA-FARBER CANCER INST · PI OSER, MATTHEW GILBERT · 2017 to 2021
$886k
NCI NIH HHS K08 CA222657NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA176745NCI NIH HHS R01 CA259273NCI NIH HHS R37 CA269990NCI NIH HHS R50 CA251956
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) exists broadly in four molecular subtypes: ASCL1, NEUROD1, POU2F3 and Inflammatory. Initially, SCLC subtypes were thought to be mutually exclusive, but recent evidence shows intra-tumoural subtype heterogeneity and plasticity between subtypes. Here, using a CRISPR-based autochthonous SCLC genetically engineered mouse model to study the consequences of KDM6A/UTX inactivation, we show that KDM6A inactivation induced plasticity from ASCL1 to NEUROD1 resulting in SCLC tumours that express both ASCL1 and NEUROD1. Mechanistically, KDM6A normally maintains an active chromatin state that favours the ASCL1 subtype with its loss decreasing H3K4me1 and increasing H3K27me3 at enhancers of neuroendocrine genes leading to a cell state that is primed for ASCL1-to-NEUROD1 subtype switching. This work identifies KDM6A as an epigenetic regulator that controls ASCL1 to NEUROD1 subtype plasticity and provides an autochthonous SCLC genetically engineered mouse model to model ASCL1 and NEUROD1 subtype heterogeneity and plasticity, which is found in 35-40% of human SCLCs.

Indexed as

Lung NeoplasmsSmall Cell Lung CarcinomaAnimalsChromatinEpigenomicsHistone DemethylasesHumansMiceChromatinHistone Demethylases

Identifiers

PMID37591951
PMCPMC10546329
OpenAlexW4385948542

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.