Evidence map›Paper›PMID 35038826›Full record

Trial reportCancer research and treatment2022

Whole-Genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study.

Joonha Kwon, Jun Hyeong Lee, Young Han Lee, Jeeyun Lee, Jin-Hee Ahn, Se Hyun Kim, Seung Hyun Kim, Tae Il Kim, Kum-Hee Yun, Young Suk Park and 4 more

Open access · diamondAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer research and treatment, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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

14 authors at 7 institutions in 1 country.

Joonha KwonDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Jun Hyeong LeeDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Young Han LeeDepartment of Radiology, Yonsei University College of Medicine, Seoul, Korea.
Jeeyun LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jin-Hee AhnDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Se Hyun KimDivision of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Seung Hyun KimDepartment of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
Tae Il KimDivision of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Kum-Hee YunBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Young Suk ParkDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jeong Eun KimDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kyu Sang LeeDepartment of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Jung Kyoon ChoiDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Hyo Song KimBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Yonsei University · KRKorea Advanced Institute of Science and Technology · KRSeoul National University Bundang Hospital · KRSamsung Medical Center · KRSungkyunkwan University · KRUlsan College · KRUniversity of Ulsan · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDesmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels. MATERIALS AND

methodsWe identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response.

resultsAmong 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders.

conclusionImatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.

Indexed as

Desmoid Tumorsbeta CateninHumansImatinib MesylateMutationProspective StudiesReceptor, Notch2Retrospective StudiesRNATranscription Factor HES-1Transcriptomebeta CateninHES1 protein, humanImatinib MesylateNOTCH2 protein, humanReceptor, Notch2RNATranscription Factor HES-1Clinical trial phase IIComputational biologyFibromatosis aggressiveImatinib mesylateTranscriptomeWhole-genome sequencing

Identifiers

PMID35038826
PMCPMC9582486
OpenAlexW4205626241

What Socratic 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 Socratic graph.