Evidence map›Paper›PMID 33854184›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021

TRIM63 is a sensitive and specific biomarker for MiT family aberration-associated renal cell carcinoma.

Xiao-Ming Wang, Yuping Zhang, Rahul Mannan, Stephanie L Skala, Roshni Rangaswamy, Anya Chinnaiyan, Fengyun Su, Xuhong Cao, Sylvia Zelenka-Wang, Lisa McMurry and 14 more

Open access · greenAbstract read
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In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 45 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

24 authors at 8 institutions in 1 country.

Xiao-Ming Wang *Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Yuping Zhang *Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
Rahul MannanMichigan Center for Translational Pathology, Ann Arbor, MI, USA.ORCID 0000-0002-6642-0468
Stephanie L SkalaDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Roshni RangaswamyMichigan Center for Translational Pathology, Ann Arbor, MI, USA.
Anya ChinnaiyanMichigan Center for Translational Pathology, Ann Arbor, MI, USA.
Fengyun SuMichigan Center for Translational Pathology, Ann Arbor, MI, USA.
Xuhong CaoMichigan Center for Translational Pathology, Ann Arbor, MI, USA.
Sylvia Zelenka-WangDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Lisa McMurryDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Hong XiaoDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Daniel E SprattDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ankur R SangoiDepartment of Pathology, El Camino Hospital, Mountain View, CA, USA.
Lina ShaoDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Bryan L BetzDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Noah BrownDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Satish K TickooDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jesse K McKenneyRobert J Tomsich Pathology and Laboratory Medicine Institute, Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
Pedram ArganiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sounak GuptaMayo Clinic, Rochester, MN, USA.
Victor E ReuterDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Arul M ChinnaiyanDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Saravana M DhanasekaranDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Rohit MehraDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. mrohit@med.umich.edu.ORCID 0000-0002-6955-8884
University of Michigan · USMichigan Center for Translational Pathology · USHoward Hughes Medical Institute · USMemorial Sloan Kettering Cancer Center · USCleveland Clinic · USEl Camino Hospital · USJohns Hopkins University · USMayo Clinic in Arizona · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA046592
6 · The paper itself

Abstract

Microphthalmia-associated transcription factor (MiT) family aberration-associated renal cell carcinoma (MiTF-RCC) is a subtype of renal cell carcinoma harboring recurrent chromosomal rearrangements involving TFE3 or TFEB genes. MiTF-RCC is morphologically diverse, can histologically resemble common RCC subtypes like clear cell RCC and papillary RCC, and often poses a diagnostic challenge in genitourinary clinical and pathology practice. To characterize the MiTF-RCC at the molecular level and identify biomarker signatures associated with MiTF-RCC, we analyzed RNAseq data from MiTF-RCC, other RCC subtypes and benign kidney. Upon identifying TRIM63 as a cancer-specific biomarker in MiTF-RCC, we evaluated its expression independently by RNA in situ hybridization (RNA-ISH) in whole tissue sections from 177 RCC cases. We specifically included 31 cytogenetically confirmed MiTF-RCC cases and 70 RCC cases suspicious for MiTF-RCC in terms of clinical and morphological features, to evaluate and compare TRIM63 RNA-ISH results with the results from TFE3/TFEB fluorescence in situ hybridization (FISH), which is the current clinical standard. We confirmed that TRIM63 mRNA was highly expressed in all classes of MiTF-RCC compared to other renal tumor categories, where it was mostly absent to low. While the TRIM63 RNA-ISH and TFE3/TFEB FISH results were largely concordant, importantly, TRIM63 RNA-ISH was strongly positive in TFE3 FISH false-negative cases with RBM10-TFE3 inversion. In conclusion, TRIM63 can serve as a diagnostic marker to distinguish MiTF-RCC from other renal tumor subtypes with overlapping morphology. We suggest a combination of TFE3/TFEB FISH and TRIM63 RNA-ISH assays to improve the accuracy and efficiency of MiTF-RCC diagnosis. Accurate diagnosis of MiTF-RCC and other RCC subtypes would enable effective targeted therapy and avoid poor therapeutic response due to tumor misclassification.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsBiomarkers, TumorCarcinoma, Renal CellHumansKidney NeoplasmsMicrophthalmia-Associated Transcription FactorMuscle ProteinsOncogene FusionSensitivity and SpecificityTranslocation, GeneticTripartite Motif ProteinsUbiquitin-Protein LigasesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBiomarkers, TumorMicrophthalmia-Associated Transcription FactorMITF protein, humanMuscle ProteinsTFE3 protein, humanTFEB protein, humanTRIM63 protein, humanTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID33854184
PMCPMC8298271
OpenAlexW3155928055

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.