Evidence map›Paper›PMID 31362756›Full record

ArticleJournal of translational medicine2019

Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma.

Sudeep Banerjee, Christopher L Corless, Markku M Miettinen, Sangkyu Noh, Rowan Ustoy, Jessica L Davis, Chih-Min Tang, Mayra Yebra, Adam M Burgoyne, Jason K Sicklick

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

Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 27 citations in OpenAlex.

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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

10 authors at 5 institutions in 1 country.

Sudeep BanerjeeDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA.
Christopher L CorlessDepartment of Pathology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Markku M MiettinenLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Sangkyu NohDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA.
Rowan UstoyDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA.
Jessica L DavisDepartment of Pathology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Chih-Min TangDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA.
Mayra YebraDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA.
Adam M BurgoyneDivision of Hematology Oncology, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Jason K SicklickDivision of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, UC San Diego Health Sciences, 3855 Health Sciences Drive, Room 2313, Mail Code 0987, La Jolla, CA, 92093-0987, USA. jsicklick@ucsd.edu.
University of California, San Diego · USOregon Health & Science University · USNational Cancer Institute · USUC San Diego Health System · USUniversity of California, Los Angeles · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Targeting Drug-Resistant Cancer Stem Cell Niches of Gastrointestinal Stromal TumorR01CA226803 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2019 to 2023
$2.1M
Novel Allosteric Kinase Inhibitors Target Imatinib-Resistant GISTK08CA168999 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2014 to 2018
$888k
Defining the Germline Genomic Landscape of a Novel GIST Multi-tumor SyndromeR21CA192072 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SICKLICK, JASON KEITH · 2016 to 2017
$399k
NCI NIH HHS K08 CA168999NCI NIH HHS K08CA168999NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA226803NCI NIH HHS R01CA226803NCI NIH HHS R21 CA192072NCI NIH HHS R21CA192072
6 · The paper itself

Abstract

backgroundPlexiform fibromyxoma (PF) is a rare gastric tumor often confused with gastrointestinal stromal tumor. These so-called "benign" tumors often present with upper GI bleeding and gastric outlet obstruction. It was recently demonstrated that approximately one-third of PF have activation of the GLI1 oncogene, a transcription factor in the hedgehog (Hh) pathway, via a MALAT1-GLI1 fusion protein or GLI1 up-regulation. Despite this discovery, the biology of most PFs remains unknown.

methodsNext generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) samples of PF specimens collected from three institutions (UCSD, NCI and OHSU). Fresh frozen tissue from one tumor was utilized for in vitro assays, including quantitative RT-PCR and cell viability assays following drug treatment.

resultsEight patients with PF were identified and 5 patients' tumors were analyzed by NGS. An index case had a mono-allelic PTCH1 deletion of exons 15-24 and a second case, identified in a validation cohort, also had a PTCH1 gene loss associated with a suspected long-range chromosome 9 deletion. Building on the role of Hh signaling in PF, PTCH1, a tumor suppressor protein, functions upstream of GLI1. Loss of PTCH1 induces GLI1 activation and downstream gene transcription. Utilizing fresh tissue from the index PF case, RT-qPCR analysis demonstrated expression of Hh pathway components, SMO and GLI1, as well as GLI1 transcriptional targets, CCND1 and HHIP. In turn, short-term in vitro treatment with a Hh pathway inhibitor, sonidegib, resulted in dose-dependent cell killing.

conclusionsFor the first time, we report a novel association between PTCH1 inactivation and the development of plexiform fibromyxoma. Hh pathway inhibition with SMO antagonists may represent a target to study for treating a subset of plexiform fibromyxomas.

Indexed as

Genes, Tumor SuppressorAdolescentAdultAgedCarrier ProteinsChromosome DeletionCyclin D1ExonsFemaleFibromaHedgehog ProteinsHigh-Throughput Nucleotide SequencingHumansMaleMembrane GlycoproteinsMiddle AgedCarrier ProteinsCCND1 protein, humanCyclin D1GLI1 protein, humanHedgehog ProteinsHHIP protein, humanMALAT1 long non-coding RNA, humanMembrane GlycoproteinsPatched-1 ReceptorPTCH1 protein, humanRNA, Long NoncodingSmoothened ReceptorSMO protein, humanZinc Finger Protein GLI1Gastric massGastrointestinal stromal tumorGLI1Hedgehog pathwayNext generation sequencingPatched 1SMO inhibitorSonidegibSubmucosal tumor

Identifiers

PMID31362756
PMCPMC6668176
OpenAlexW2965027405

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LicenceCC BY
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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.