Evidence map›Paper›PMID 35738865›Full record

ArticleNeuro-oncology2023

Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas.

Holger Weishaupt, Matko Čančer, Gabriela Rosén, Karl O Holmberg, Susana Häggqvist, Ignas Bunikis, Yiwen Jiang, Smitha Sreedharan, Ulf Gyllensten, Oren J Becher and 3 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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  5. The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Holger WeishauptDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Matko ČančerDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Gabriela RosénDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Karl O HolmbergDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Susana HäggqvistDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Ignas BunikisDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Yiwen JiangDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Smitha SreedharanDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Ulf GyllenstenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Oren J BecherDepartment of Pediatrics and Biochemistry and Molecular Genetics, Northwestern University, Chicago, Illinois, USA.
Lene UhrbomDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Adam AmeurDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-6085-6749
Fredrik J SwartlingDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-8460-4367
Uppsala University · SENorthwestern University · US

Funding

European Research Council 640275
6 · The paper itself

Abstract

backgroundMalignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site.

methodsHere we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies.

resultsA large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance.

conclusionsAltogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.

Indexed as

Brain NeoplasmsGliomaAdaptor Proteins, Signal TransducingAnimalsGenetic Association StudiesHumansMiceOncogenesProto-Oncogene Proteins c-sisAdaptor Proteins, Signal TransducingPPFIBP1 protein, humanProto-Oncogene Proteins c-sisforward genetics screenglioblastomaliprin-beta-1PDGFBRCAS

Identifiers

PMID35738865
PMCPMC9825320
OpenAlexW4283366822

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.