Evidence map›Paper›PMID 36082904›Full record

ArticleThe oncologist2023

Comprehensive Landscape of Cyclin Pathway Gene Alterations and Co-occurrence with FGF/FGFR Aberrations Across Urinary Tract Tumors.

Denis L F Jardim, Sherri Z Millis, Jeffrey S Ross, Scott Lippman, Siraj M Ali, Razelle Kurzrock

Open access · goldAbstract read
In one paragraph

Article in The oncologist, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

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  4. Review
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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

6 authors at 5 institutions in 2 countries.

Denis L F JardimDepartment of Clinical Oncology, Hospital Sirio Libanes, São Paulo, Brazil.ORCID 0000-0003-4663-1521
Sherri Z MillisFoundation Medicine, Cambridge, MA, USA.
Jeffrey S RossFoundation Medicine, Cambridge, MA, USA.
Scott LippmanCenter for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA, USA.
Siraj M AliFoundation Medicine, Cambridge, MA, USA.
Razelle KurzrockWIN Consortium for Personalized Cancer Therapy, Paris, France.
Foundation Medicine (United States)Eastern Cooperative Oncology Group · USMedical College of Wisconsin · USSUNY Upstate Medical University · USUniversity of California San Diego · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundCyclin pathway gene alterations are frequent in urothelial tumors and may co-exist with other important aberrations, leading to therapeutic opportunities. We characterized the landscape of cyclin gene alterations in urothelial and non-urothelial urinary tract (UT) malignancies. PATIENTS AND

methodsOverall, 6842 urothelial and 897 non-urothelial UT cancers were analyzed (hybrid-capture-based comprehensive genomic profile (Foundation Medicine)). Alteration frequency in cyclin-sensitizing and -resistance genes, and co-occurrence with fibroblast growth factor receptor (FGFR) gene abnormalities were evaluated.

resultsCyclin-activating gene alterations were detected in 47.3% of urothelial and 37.9% of non-urothelial UT cancers. Frequency varied by histology and tumor site. CDKN2A and CDKN2B loss were the most frequent alterations in urothelial tumors (present in 38.5% and 30.4% of patients, respectively). Both genes were less frequently altered in adenocarcinomas (15.2% and 8.9%), but commonly altered in squamous cell carcinomas (74.4% and 39%). Tumors of neuroendocrine origin were relatively silent in activating cyclin alterations, but frequently displayed Rb1 alterations (86% and 83.7% of neuroendocrines and small cell carcinomas). Urachal tumors (n = 79) presented a distinct landscape of cyclin alterations relative to other UT cancers, with less frequent alterations overall. FGF/FGFR genes were altered in 34.9% of urothelial (22.1% in FGFR3), and 19.4% of non-urothelial urinary tract tumors (6.8% FGFR3). Cyclin-activating alterations frequently co-occurred with FGF/FGFR alterations but were in general mutually exclusively with cyclin resistance alterations (RB1/CCNE1).

conclusionsCyclin pathway activating alterations are common in urinary tract tumors, but frequency varies with histology and tumors sites. Co-occurrence of cyclin and FGFR pathway alterations may inform therapeutic opportunities.

Indexed as

Urinary Bladder NeoplasmsUrologic NeoplasmsCell Cycle CheckpointsCyclinsFibroblast Growth FactorsHumansReceptors, Fibroblast Growth FactorCyclinsFibroblast Growth FactorsReceptors, Fibroblast Growth FactorCDK4CDK6cell cyclemolecular geneticsprecision oncology targeted therapy

Identifiers

PMID36082904
PMCPMC9907036
OpenAlexW4295066688

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.