Evidence map›Paper›PMID 38367620›Full record

ArticleAmerican journal of human genetics2024

Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA.

Yige Li, Jingwen Gong, Qingrong Sun, Eu Gene Vong, Xiaoqing Cheng, Binghong Wang, Ying Yuan, Li Jin, Eric R Gamazon, Dan Zhou and 2 more

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

Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

12 authors at 8 institutions in 2 countries.

Yige LiDepartment of Pathology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Jingwen GongDepartment of Pathology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, Zhejiang Province, China.
Qingrong SunDepartment of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, Zhejiang Province, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, Zhejiang Province, China; College of Information Science and Technology, ZheJiang Shuren University, Hangzhou 310015, ZheJiang, China.
Eu Gene VongDepartment of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Xiaoqing ChengDepartment of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Binghong WangSir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Ying YuanDepartment of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Li JinState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China; Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, China.
Eric R GamazonDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Data Science Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Dan ZhouVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Maode LaiDepartment of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, Zhejiang Province, China; Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: lmd@zju.edu.cn.
Dandan ZhangDepartment of Pathology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, Zhejiang Province, China; Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: dandanz@zju.edu.cn.
Second Affiliated Hospital of Zhejiang University · CNSir Run Run Shaw Hospital · CNZhejiang Chinese Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNVanderbilt Psychiatric Hospital · USVanderbilt University Medical Center · USZhejiang Cancer Hospital · CNZhejiang Shuren University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetic variants are involved in the orchestration of alternative polyadenylation (APA) events, while the role of DNA methylation in regulating APA remains unclear. We generated a comprehensive atlas of APA quantitative trait methylation sites (apaQTMs) across 21 different types of cancer (1,612 to 60,219 acting in cis and 4,448 to 142,349 in trans). Potential causal apaQTMs in non-cancer samples were also identified. Mechanistically, we observed a strong enrichment of cis-apaQTMs near polyadenylation sites (PASs) and both cis- and trans-apaQTMs in proximity to transcription factor (TF) binding regions. Through the integration of ChIP-signals and RNA-seq data from cell lines, we have identified several regulators of APA events, acting either directly or indirectly, implicating novel functions of some important genes, such as TCF7L2, which is known for its involvement in type 2 diabetes and cancers. Furthermore, we have identified a vast number of QTMs that share the same putative causal CpG sites with five different cancer types, underscoring the roles of QTMs, including apaQTMs, in the process of tumorigenesis. DNA methylation is extensively involved in the regulation of APA events in human cancers. In an attempt to elucidate the potential underlying molecular mechanisms of APA by DNA methylation, our study paves the way for subsequent experimental validations into the intricate biological functions of DNA methylation in APA regulation and the pathogenesis of human cancers. To present a comprehensive catalog of apaQTM patterns, we introduce the Pancan-apaQTM database, available at https://pancan-apaqtm-zju.shinyapps.io/pancanaQTM/.

Indexed as

Diabetes Mellitus, Type 2Neoplasms3' Untranslated RegionsDNA MethylationGene Expression RegulationHumansPolyadenylation3' Untranslated Regionsalternative polyadenylationand colocalizationcis-regulationDNA methylationhuman cancerMendelian randomization analysispan-cancer analysispost-transcriptionquantitative trait methylation sitestrans-regulation

Identifiers

PMID38367620
PMCPMC10940021
OpenAlexW4391888108

What OpenQuestion holds

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Registered trials

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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.