Evidence map›Paper›PMID 34706158›Full record

ArticleMolecular oncology2022

Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence.

Le Yu, Dan Zhou, Guiming Zhang, Zhonglu Ren, Xin Luo, Peng Liu, Steven W Plouffe, Zhipeng Meng, Toshiro Moroishi, Yilei Li and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Co-occurrence ofAmerican journal of ophthalmology case reports · 2025
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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

14 authors at 6 institutions in 3 countries.

Le YuSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.ORCID 0000-0002-9773-1162
Dan ZhouSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Guiming ZhangSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Zhonglu RenCollege of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou, China.
Xin LuoSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Peng LiuInstitutes of Biomedical Sciences, Fudan University, Shanghai, China.
Steven W PlouffeDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, CA, USA.
Zhipeng MengDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, CA, USA.
Toshiro MoroishiDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, CA, USA.
Yilei LiDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yiyue ZhangDivision of Cell, Development and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, China.
Joan Heller BrownDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, CA, USA.
Shuwen LiuSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Kun-Liang GuanDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, CA, USA.
Southern Medical University · CNUniversity of California San Diego · USFudan University · CNGuangdong Pharmaceutical University · CNNanfang Hospital · CNSouth China University of Technology · CN

Funding

Molecular and Genetic Determinants of Invasion in HNSCCR01DE015964 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, CUN-YU · 2004 to 2019
$6.6M
Molecular Mechanism and Therapy for Ocular MelanomaR01CA217642 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2017 to 2022
$2.4M
RhoA and GPCR mediated transcriptional activation regulates glioblastomaR01CA218859 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2018 to 2022
$2.3M
NCI NIH HHS R01 CA217642NCI NIH HHS R01 CA218859NIDCR NIH HHS R01 DE015964
6 · The paper itself

Abstract

Uveal melanoma (UM) is the most common intraocular tumor in adults. Recurrent mutations in BRCA1-associated protein 1 (BAP1) and splicing factor 3B subunit 1 (SF3B1) display a mutually exclusive pattern in UM, but the underlying mechanism is unknown. We show that combined BAP1 deficiency and SF3B1 hotspot mutation lead to senescence and growth arrest in human UM cells. Although p53 protein expression is induced, deletion of TP53 (encoding p53) only modestly rescues the observed senescent phenotype. UM cells with BAP1 loss or SF3B1 mutation are more sensitive to chemotherapeutic drugs compared with their isogenic parental cells. Transcriptome analysis shows that DNA-repair genes are downregulated upon co-occurrence of BAP1 deletion and SF3B1 mutation, thus leading to impaired DNA damage response and the induction of senescence. The co-occurrence of these two mutations reduces invasion of UM cells in zebrafish xenograft models and suppresses growth of melanoma xenografts in nude mice. Our findings provide a mechanistic explanation for the mutual exclusivity of BAP1 and SF3B1 mutations in human UM.

Indexed as

MelanomaPhosphoproteinsRNA Splicing FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseUveal NeoplasmsAnimalsCellular SenescenceDNA Mutational AnalysisHumansMiceMice, NudeMutationUveal MelanomaZebrafishBAP1 protein, humanPhosphoproteinsRNA Splicing FactorsSF3B1 protein, humanTumor Suppressor ProteinsUbiquitin ThiolesteraseBAP1mutually exclusive patternrecurrent mutationssenescenceSF3B1uveal melanoma

Identifiers

PMID34706158
PMCPMC8807356
OpenAlexW3209337249

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.