Evidence map›Paper›PMID 37205492›Full record

ArticlebioRxiv : the preprint server for biology2023

Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma.

Damon A Hofman, Jorge Ruiz-Orera, Ian Yannuzzi, Rakesh Murugesan, Adam Brown, Karl R Clauser, Alexandra L Condurat, Jip T van Dinter, Sem A G Engels, Amy Goodale and 14 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 8 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 3 countries.

Damon A HofmanPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands.
Jorge Ruiz-OreraCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Ian YannuzziBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Rakesh MurugesanBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Adam BrownBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Karl R ClauserBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Alexandra L ConduratBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jip T van DinterPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands.
Sem A G EngelsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands.
Amy GoodaleBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jasper van der LugtPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands.
Tanaz AbidBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Li WangBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Kevin N ZhouDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jayne VogelzangDepartment of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
Keith L LigonDepartment of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
Timothy N PhoenixDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45229, USA.
Jennifer A RothBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
David E RootBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Norbert HubnerCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Pratiti BandopadhayayBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Sebastiaan van HeeschPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands.
John R PrensnerBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Broad Institute · USPrincess Máxima Center · NLBrigham and Women's Hospital · USMax Delbrück Center · DEKaiser Permanente · USUniversity of Cincinnati Medical Center · US

Funding

Making cancer precision medicine real: bottlenecks and opportunitiesR35CA242457 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2019 to 2025
$6.9M
Deciphering non-canonical translation in high risk medulloblastomaK08CA263552 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Prensner · 2022 to 2026
$1.2M
NCI NIH HHS K08 CA263552NCI NIH HHS R35 CA242457
6 · The paper itself

Abstract

A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames. To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a step-wise approach to employ multiple CRISPR-Cas9 screens to elucidate functional non-canonical ORFs implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream open reading frames (uORFs) exhibited selective functionality independent of the main coding sequence. One of these, ASNSD1-uORF or ASDURF, was upregulated, associated with the MYC family oncogenes, and was required for medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future cancer genomics studies seeking to define new cancer targets.

Indexed as

CancerCRISPRgene dependencylncRNAsmedulloblastomanon-canonical ORFsRibo-seqtranslational regulationuORF

Identifiers

PMID37205492
PMCPMC10187264
OpenAlexW4375868177

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.