Evidence map›Paper›PMID 34065218›Full record

ArticleCancers2021

Inactivating Mutations of the

Chao Gao, Guangxu Jin, Elizabeth Forbes, Lingegowda S Mangala, Yingmei Wang, Cristian Rodriguez-Aguayo, Paola Amero, Emine Bayraktar, Ye Yan, Gabriel Lopez-Berestein and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. 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
0.1field-weighted citation impact, top 63% 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. Article
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 4 institutions in 2 countries.

Chao GaoDepartment of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.ORCID 0000-0002-9200-6164
Guangxu JinDepartment of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.
Elizabeth ForbesDepartment of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.
Lingegowda S MangalaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Yingmei WangDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
Cristian Rodriguez-AguayoCenter for RNA Interference and Non-Coding RNAs, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-7880-7723
Paola AmeroDepartment of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-7503-0381
Emine BayraktarDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Ye YanDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
Gabriel Lopez-BeresteinCenter for RNA Interference and Non-Coding RNAs, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Russell R BroaddusDepartment of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Fengxia XueDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
Wei ZhangDepartment of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.
The University of Texas MD Anderson Cancer Center · USAtrium Health Wake Forest Baptist · USTianjin Medical University General Hospital · CNUniversity of North Carolina at Chapel Hill · US

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Targeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BROADDUS, RUSSELL R · 2003 to 2020
$32.0M
NCI NIH HHS 2P50CA098258NCI NIH HHS P30 CA012197NCI NIH HHS P50 CA098258
6 · The paper itself

Abstract

IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK's role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.

Indexed as

cisplatinDNA repairendometrial cancerIKKu80somatic mutation

Identifiers

PMID34065218
PMCPMC8160817
OpenAlexW3163947754

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.