Evidence map›Paper›PMID 31043681›Full record

ArticleProstate cancer and prostatic diseases2019

Characterization of a KLK2-FGFR2 fusion gene in two cases of metastatic prostate cancer.

Melanie A Krook, Hannah Barker, Hui-Zi Chen, Julie W Reeser, Michele R Wing, Dorrelyn Martin, Amy M Smith, Thuy Dao, Russell Bonneville, Eric Samorodnitsky and 5 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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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

15 authors at 1 institution in 1 country.

Melanie A KrookComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Hannah BarkerComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Hui-Zi ChenComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Julie W ReeserComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Michele R WingComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Dorrelyn MartinComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.ORCID http://orcid.org/0000-0002-9622-9402
Amy M SmithComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Thuy DaoComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Russell BonnevilleComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Eric SamorodnitskyComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Jharna MiyaComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Aharon G FreudComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
J Paul MonkComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Steven K ClintonComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Sameek RoychowdhuryComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. Sameek.Roychowdhury@osumc.edu.
The Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI WANCAI YANG · 1985 to 2026
$132.3M
ONOCOLOGY TRAINING GRANTT32CA009338 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C., POLLOCK, RAPHAEL E. · 1985 to 2018
$8.3M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NRSA Training CoreTL1TR002735 · NCATS · OHIO STATE UNIVERSITY · PI BUMGARDNER, GINNY L, KIRSCHNER, LAWRENCE S · 2018 to 2022
$1.3M
Genomic characterization of tumor heterogeneity in recurrent small cell lung cancer through research autopsyK08CA241309 · NCI · OHIO STATE UNIVERSITY · PI CHEN, HUI-ZI · 2019 to 2023
$1.2M
Assay Validation of Targeted RNA sequencing to Detect Kinase Gene FusionsUH3CA202971 · NCI · OHIO STATE UNIVERSITY · PI ROYCHOWDHURY, SAMEEK · 2018 to 2020
$976k
Detection of microsatellite instability biomarkers for therapeutic clinical trial eligibilityUH2CA216432 · NCI · OHIO STATE UNIVERSITY · PI ROYCHOWDHURY, SAMEEK · 2017 to 2017
$354k
Assay Validation of Targeted RNA sequencing to Detect Kinase Gene FusionsUH2CA202971 · NCI · OHIO STATE UNIVERSITY · PI ROYCHOWDHURY, SAMEEK · 2016 to 2016
$352k
American Cancer Society (American Cancer Society, Inc.) MRSG-12-194-01-TBGNCATS NIH HHS TL1 TR002735NCI NIH HHS K08 CA241309NCI NIH HHS P30 CA016058NCI NIH HHS T32 CA009338NCI NIH HHS UH2 CA202971NCI NIH HHS UH2 CA216432NCI NIH HHS UH3 CA202971NIGMS NIH HHS T32 GM068412U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5T32CA009338U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32 T32GM068412U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) UH2CA202971
6 · The paper itself

Abstract

backgroundThe fibroblast growth factor receptor (FGFR) signaling pathway is activated in multiple tumor types through gene amplifications, single base substitutions, or gene fusions. Multiple small molecule kinase inhibitors targeting FGFR are currently being evaluated in clinical trials for patients with FGFR chromosomal translocations. Patients with novel gene fusions involving FGFR may represent candidates for kinase inhibitors.

methodsA targeted RNA-sequencing assay identified a KLK2-FGFR2 fusion gene in two patients with metastatic prostate cancer. NIH3T3 cells were transduced to express the KLK2-FGFR2 fusion. Migration assays, Western blots, and drug sensitivity assays were performed to functionally characterize the fusion.

resultsExpression of the KLK2-FGFR2 fusion protein in NIH3T3 cells induced a profound morphological change promoting enhanced migration and activation of downstream proteins in FGFR signaling pathways. The KLK2-FGFR2 fusion protein was determined to be highly sensitive to the selective FGFR inhibitors AZD-4547, BGJ398, JNJ-42756943, the irreversible inhibitor TAS-120, and the non-selective inhibitor Ponatinib. The KLK2-FGFR2 fusion did not exhibit sensitivity to the non-selective inhibitor Dovitinib.

conclusionsImportantly, the KLK2-FGFR2 fusion represents a novel target for precision therapies and should be screened for in men with prostate cancer.

Indexed as

AnimalsCarcinogenesisCell MovementHEK293 CellsHumansKallikreinsMaleMiceMiddle AgedMolecular Targeted TherapyNIH 3T3 CellsOncogene Proteins, FusionPrecision MedicineProstatic NeoplasmsProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 2FGFR2 protein, humanKallikreinsKLK2 protein, humanOncogene Proteins, FusionProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 2Recombinant Fusion Proteins

Identifiers

PMID31043681
PMCPMC6824932
OpenAlexW2943135814

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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.