Evidence map›Paper›PMID 40369102›Full record

ArticleNPJ precision oncology2025

Tumor break load quantitates structural variant-associated genomic instability with biological and clinical relevance across cancers.

Soufyan Lakbir, Renske de Wit, Ino de Bruijn, Ritika Kundra, Ramyasree Madupuri, Jianjiong Gao, Nikolaus Schultz, Gerrit A Meijer, Jaap Heringa, Remond J A Fijneman and 1 more

Abstract read
In one paragraph

Article in NPJ precision oncology, 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
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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

11 authors.

Soufyan LakbirBioinformatics Section, Department of Computer Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Renske de WitTranslational Gastrointestinal Oncology Group, Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ino de BruijnMemorial Sloan Kettering Cancer Center, New York City, NY, USA.
Ritika KundraMemorial Sloan Kettering Cancer Center, New York City, NY, USA.
Ramyasree MadupuriMemorial Sloan Kettering Cancer Center, New York City, NY, USA.
Jianjiong GaoMemorial Sloan Kettering Cancer Center, New York City, NY, USA.
Nikolaus SchultzMemorial Sloan Kettering Cancer Center, New York City, NY, USA.
Gerrit A MeijerTranslational Gastrointestinal Oncology Group, Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jaap HeringaBioinformatics Section, Department of Computer Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Remond J A FijnemanTranslational Gastrointestinal Oncology Group, Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. r.fijneman@nki.nl.
Sanne AbelnBioinformatics Section, Department of Computer Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. s.abeln@uu.nl.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Health~Holland LSHM19027Health~Holland LSHM21018NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

While structural variants (SVs) are a clear sign of genomic instability, they have not been systematically quantified per patient since declining costs have only recently enabled large-scale profiling. Therefore, the biological and clinical impact of high numbers of SVs in patients is unknown. We introduce tumor break load (TBL), defined as the sum of unbalanced SVs, as a measure for SV-associated genomic instability. Using pan-cancer data from TCGA, PCAWG, and CCLE, we show that a high TBL is associated with significant changes in gene expression in 26/31 cancer types that consistently involve upregulation of DNA damage repair and downregulation of immune response pathways. Patients with a high TBL show a higher risk of recurrence and shorter median survival times for 5/15 cancer types. Our data demonstrate that TBL is a biologically and clinically relevant feature of genomic instability that may aid patient prognostication and treatment stratification. For the datasets analyzed in this study, TBL has been made available in cBioPortal.

Identifiers

PMID40369102
PMCPMC12078582

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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.