Evidence map›Paper›PMID 41015032›Full record

ArticleCell reports. Medicine2025

Chromosomal instability degrades developmental phenotypes essential for anti-GD2 immunotherapy outcomes in high-risk neuroblastoma.

Ryan James Rebernick, Jae Eun Choi, Calvin Hesse, Noshad Hosseini, Alec Chu, Jin Zhou, Yu Ning, Rui Wang, Xuhong Cao, Meredith Irwin and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. 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

17 authors.

Ryan James RebernickDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Jae Eun ChoiMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Calvin HesseDepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Noshad HosseiniDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Alec ChuMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Jin ZhouMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Yu NingMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Rui WangMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xuhong CaoMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Meredith IrwinDepartment of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Yi-Mi WuMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Chandan KumarMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Raja RabahDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Rochelle BagatellDepartment of Pediatrics, Perelman School of Medicine and Abramson Cancer Center, University of Pennsylvania Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: arul@med.umich.edu.
Rajen ModyMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: rmody@med.umich.edu.
Marcin CieslikDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mcieslik@med.umich.edu.

Funding

NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6M
COG SDMC - Statistics CoreU10CA180899 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TODD A ALONZO · 2014 to 2026
$132.8M
COG U24 Funding 2026-2027U24CA196173 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Mignon Lee-Cheun Loh, Nilsa Del Carmen Ramirez Milan · 2015 to 2026
$62.5M
Exploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4M
Dissecting the mechanisms by which chromosomal instability impacts anti-Disialoganglioside responses in neuroblastomaF30CA275039 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REBERNICK, RYAN · 2022 to 2024
$158k
NCI NIH HHS F30 CA275039NCI NIH HHS R35 CA231996NCI NIH HHS U10 CA180886NCI NIH HHS U10 CA180899NCI NIH HHS U24 CA196173
6 · The paper itself

Abstract

High-risk neuroblastoma (HR-NBL) is a pediatric malignancy that arises during sympathoadrenal development and expresses the surface disialoganglioside GD2. Monoclonal anti-GD2 immunotherapy is a mainstay of HR-NBL treatment; however, it is associated with severe toxicities. Genomic correlates of outcomes following multimodality therapy containing anti-GD2 immunotherapy are limited. We profile 840 tumors and identify actionable ALK gene fusions in HR-NBL. We leverage fetal sympathoadrenal single-cell RNA sequencing to characterize patients with improved post-multimodality outcomes. We demonstrate that patients with improved outcomes have tumors that upregulate noradrenergic and metabolic phenotypes characteristic of mature sympathoblasts-a fetal sympathoadrenal cell population. We show that loss of these developmental phenotypes is mediated by chromosome 11q loss. Targeted analysis of 19 biopsy pairs identifies significant clonal evolution and accumulation of cell-cycle mutations following multimodality treatment. Collectively, we identify chromosomal instability-specifically 11q loss-as key in degrading developmental phenotypes critical for outcomes following multimodality therapy containing anti-GD2 immunotherapy.

Indexed as

Chromosomal InstabilityGangliosidesImmunotherapyNeuroblastomaChromosomes, Human, Pair 11FemaleHumansMalePhenotypeTreatment Outcomeganglioside, GD2Gangliosidesanti-GD2chromosomal instabilitydisialogangliosideimmunotherapymultimodality therapyneuroblastneuroblastomaneuroendocrinesympathoadrenalsympathoblast

Identifiers

PMID41015032
PMCPMC12629816

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.