PortalPublikationenTFE3 activation in a TSC1-altered malignant PEComa: challeng...

TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms

Standard

TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms. / Schmiester, Maren; Dolnik, Anna; Kornak, Uwe; Pfitzner, Berit; Hummel, Michael; Treue, Denise; Hartmann, Arndt; Agaimy, Abbas; Weyerer, Veronika; Lekaj, Anja; Brakemeier, Susanne; Peters, Robert; Öllinger, Robert; Märdian, Sven; Bullinger, Lars; Striefler, Jana Käthe; Flörcken, Anne.

in: J PATHOL CLIN RES, Jahrgang 7, Nr. 1, 01.2021, S. 3-9.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schmiester, M, Dolnik, A, Kornak, U, Pfitzner, B, Hummel, M, Treue, D, Hartmann, A, Agaimy, A, Weyerer, V, Lekaj, A, Brakemeier, S, Peters, R, Öllinger, R, Märdian, S, Bullinger, L, Striefler, JK & Flörcken, A 2021, 'TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms', J PATHOL CLIN RES, Jg. 7, Nr. 1, S. 3-9. https://doi.org/10.1002/cjp2.187

APA

Schmiester, M., Dolnik, A., Kornak, U., Pfitzner, B., Hummel, M., Treue, D., Hartmann, A., Agaimy, A., Weyerer, V., Lekaj, A., Brakemeier, S., Peters, R., Öllinger, R., Märdian, S., Bullinger, L., Striefler, J. K., & Flörcken, A. (2021). TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms. J PATHOL CLIN RES, 7(1), 3-9. https://doi.org/10.1002/cjp2.187

Vancouver

Schmiester M, Dolnik A, Kornak U, Pfitzner B, Hummel M, Treue D et al. TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms. J PATHOL CLIN RES. 2021 Jan;7(1):3-9. https://doi.org/10.1002/cjp2.187

Bibtex

@article{0bc5d79c3a624092917ea1173b19f3a2,
title = "TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms",
abstract = "Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1-mutated PEComa displaying a TFE3-altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2-mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.",
keywords = "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics, Biomarkers, Tumor/genetics, DNA Copy Number Variations, Disease Progression, Fatal Outcome, Female, Gene Amplification, Gene Expression Profiling, Genetic Predisposition to Disease, Humans, In Situ Hybridization, Fluorescence, Kidney Neoplasms/genetics, Middle Aged, Mutation, Perivascular Epithelioid Cell Neoplasms/genetics, Phenotype, Transcriptional Activation, Treatment Outcome, Tuberous Sclerosis Complex 1 Protein/genetics, Whole Genome Sequencing",
author = "Maren Schmiester and Anna Dolnik and Uwe Kornak and Berit Pfitzner and Michael Hummel and Denise Treue and Arndt Hartmann and Abbas Agaimy and Veronika Weyerer and Anja Lekaj and Susanne Brakemeier and Robert Peters and Robert {\"O}llinger and Sven M{\"a}rdian and Lars Bullinger and Striefler, {Jana K{\"a}the} and Anne Fl{\"o}rcken",
note = "{\textcopyright} 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.",
year = "2021",
month = jan,
doi = "10.1002/cjp2.187",
language = "English",
volume = "7",
pages = "3--9",
journal = "J PATHOL CLIN RES",
issn = "2056-4538",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms

AU - Schmiester, Maren

AU - Dolnik, Anna

AU - Kornak, Uwe

AU - Pfitzner, Berit

AU - Hummel, Michael

AU - Treue, Denise

AU - Hartmann, Arndt

AU - Agaimy, Abbas

AU - Weyerer, Veronika

AU - Lekaj, Anja

AU - Brakemeier, Susanne

AU - Peters, Robert

AU - Öllinger, Robert

AU - Märdian, Sven

AU - Bullinger, Lars

AU - Striefler, Jana Käthe

AU - Flörcken, Anne

N1 - © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

PY - 2021/1

Y1 - 2021/1

N2 - Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1-mutated PEComa displaying a TFE3-altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2-mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.

AB - Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1-mutated PEComa displaying a TFE3-altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2-mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.

KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics

KW - Biomarkers, Tumor/genetics

KW - DNA Copy Number Variations

KW - Disease Progression

KW - Fatal Outcome

KW - Female

KW - Gene Amplification

KW - Gene Expression Profiling

KW - Genetic Predisposition to Disease

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Kidney Neoplasms/genetics

KW - Middle Aged

KW - Mutation

KW - Perivascular Epithelioid Cell Neoplasms/genetics

KW - Phenotype

KW - Transcriptional Activation

KW - Treatment Outcome

KW - Tuberous Sclerosis Complex 1 Protein/genetics

KW - Whole Genome Sequencing

U2 - 10.1002/cjp2.187

DO - 10.1002/cjp2.187

M3 - SCORING: Journal article

C2 - 33180365

VL - 7

SP - 3

EP - 9

JO - J PATHOL CLIN RES

JF - J PATHOL CLIN RES

SN - 2056-4538

IS - 1

ER -