Evidence map›Paper›PMID 38912901›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024

Detecting Small Cell Transformation in Patients with Advanced EGFR Mutant Lung Adenocarcinoma through Epigenomic cfDNA Profiling.

Talal El Zarif, Catherine B Meador, Xintao Qiu, Ji-Heui Seo, Matthew P Davidsohn, Hunter Savignano, Gitanjali Lakshminarayanan, Heather M McClure, John Canniff, Brad Fortunato and 15 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

  1. Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026
    Review
  2. Article
  3. JTO clinical and research reports · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Precision Oncology 2.0: Guiding Magic Bullets With Expression-Based Liquid Biopsy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Talal El Zarif *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-4507-2396
Catherine B Meador *Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5006-3569
Xintao Qiu *Department of Medicine, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0002-8560-7017
Ji-Heui SeoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-7280-3334
Matthew P DavidsohnDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0000-1480-9423
Hunter SavignanoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0007-9138-9363
Gitanjali LakshminarayananDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-6386-8478
Heather M McClureDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-4441-5609
John CanniffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0003-2954-4730
Brad FortunatoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0000-6545-4351
Rong LiCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0000-1046-9580
Mandeep K BanwaitDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-4789-0293
Karl SemaanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0004-2315-8422
Marc EidDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-4738-5695
Henry LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6849-6629
Yin P HungDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-8568-1591
Navin R MahadevanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-6805-8861
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-5422-4275
Matthew G OserDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2047-0969
Zofia PiotrowskaDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9008-8573
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-9201-3217
Sylvan C BacaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-4087-8606
Aaron N HataDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-6127-318X
Matthew L Freedman *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-0151-1238
Jacob E Berchuck *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-7607-2428

Funding

The Activation of ERBB3 Signaling as a Resistance Mechanism to Targeted TherapiesR01CA137008 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Aaron N Hata, ZOFIA PIOTROWSKA · 2009 to 2026
$5.7M
Elucidation of the genetic mechanisms driving prostate tumorigenesis through integrative computational and functional approachesR01CA251555 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, PASANIUC, BOGDAN · 2021 to 2025
$3.4M
Elucidating prostate cancer risk mechanisms through large-scale cistrome wide association studiesR01CA262577 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, GIMELBRANT, ALEXANDER · 2022 to 2025
$3.3M
Targeting the immunologic vulnerabilities of small cell lung carcinomaK08CA270077 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Navin Mahadevan · 2022 to 2026
$1.0M
American Cancer Society (ACS) 2022A019104Claudia Adams Barr Program for Innovative Cancer ResearchCongressionally Directed Medical Research Programs (CDMRP) W81XWH-21-1-0339Cutler Family Fund for Prevention and Early DetectionDamon Runyon Cancer Research Foundation (DRCRF)Dana-Farber Cancer Institute Presidential Initiatives FundDana-Farber/Harvard Cancer Center (DF/HCC) Center Lung Cancer SPORE Research Development AwardDOD Prostate Cancer Research Program (PCRP) W81XWH-20-1-0118DOD Prostate Cancer Research Program (PCRP) W81XWH-21-1-0358Donahue Family FundFund for Innovation in Cancer Informatics (ICI)H.L. Snyder Medical Research FoundationKure It Cancer Research FoundationLUNGSTRONG FoundationNational Cancer Institute (NCI) K08CA270077National Cancer Institute (NCI) R01CA137008National Cancer Institute (NCI) R01CA262577NCI NIH HHS K08 CA270077NCI NIH HHS R01 CA137008NCI NIH HHS R01 CA251555NCI NIH HHS R01 CA262577Pan-Mass Challenge Team 3GProstate Cancer Foundation (PCF) Movember PCF Challenge AwardThe Dave Page Cancer Research Fund
6 · The paper itself

Abstract

purposeHistologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sought to develop an epigenomic cell-free DNA (cfDNA)-based approach to noninvasively detect small cell transformation in patients with EGFR mutant (EGFRm) LUAD. EXPERIMENTAL

designTo characterize the epigenomic landscape of transformed (t)SCLC relative to LUAD and de novo SCLC, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to profile the histone modifications H3K27ac, H3K4me3, and H3K27me3; methylated DNA immunoprecipitation sequencing (MeDIP-seq); assay for transposase-accessible chromatin sequencing; and RNA sequencing on 26 lung cancer patient-derived xenograft (PDX) tumors. We then generated and analyzed H3K27ac ChIP-seq, MeDIP-seq, and whole genome sequencing cfDNA data from 1 mL aliquots of plasma from patients with EGFRm LUAD with or without tSCLC.

resultsAnalysis of 126 epigenomic libraries from the lung cancer PDXs revealed widespread epigenomic reprogramming between LUAD and tSCLC, with a large number of differential H3K27ac (n = 24,424), DNA methylation (n = 3,298), and chromatin accessibility (n = 16,352) sites between the two histologies. Tumor-informed analysis of each of these three epigenomic features in cfDNA resulted in accurate noninvasive discrimination between patients with EGFRm LUAD versus tSCLC [area under the receiver operating characteristic curve (AUROC) = 0.82-0.87]. A multianalyte cfDNA-based classifier integrating these three epigenomic features discriminated between EGFRm LUAD versus tSCLC with an AUROC of 0.94.

conclusionsThese data demonstrate the feasibility of detecting small cell transformation in patients with EGFRm LUAD through epigenomic cfDNA profiling of 1 mL of patient plasma.

Indexed as

Adenocarcinoma of LungCell-Free Nucleic AcidsEpigenomicsErbB ReceptorsLung NeoplasmsMutationAnimalsBiomarkers, TumorCell Transformation, NeoplasticDNA MethylationEpigenesis, GeneticFemaleHumansMaleMiceSmall Cell Lung CarcinomaBiomarkers, TumorCell-Free Nucleic AcidsEGFR protein, humanErbB Receptors

Identifiers

PMID38912901
PMCPMC11369616

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.