Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation

Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marion Wobser, Sabine Roth, Silke Appenzeller, Roland Houben, David Schrama, Matthias Goebeler, Eva Geissinger, Andreas Rosenwald, Katja Maurus
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mycosis fungoides cutaneous T-cell-lymphoma panel sequencing large cell transformation CD30 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/15afe10b47fb451e98654f4fce88d87d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15afe10b47fb451e98654f4fce88d87d
record_format	dspace
spelling	oai:doaj.org-article:15afe10b47fb451e98654f4fce88d87d2021-11-11T15:33:47ZTargeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation10.3390/cancers132155122072-6694https://doaj.org/article/15afe10b47fb451e98654f4fce88d87d2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5512https://doaj.org/toc/2072-6694Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). The analyzed patients were attributed to three different groups based on the presence of LCT and clinical behavior. Results: While indolent MF cases without LCT did not show pathogenic driver mutations, a high rate of oncogenic alterations was detected in patients with LCT and aggressive clinical courses. Various genes of different oncogenic signaling pathways, including the MAPK and JAK-STAT signaling pathways, as well as epigenetic modifiers were affected. A high inter-individual and distinctive intra-individual mutation diversity was observed. Oncogenic RAS mutations were exclusively detected in patients with LCT. Conclusion: Our data demonstrate that LCT transition of MF is associated with increased frequency of somatic mutations in cancer-associated genes. In particular, the activation of RAS signaling—together with epigenetic dysregulation—may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior.Marion WobserSabine RothSilke AppenzellerRoland HoubenDavid SchramaMatthias GoebelerEva GeissingerAndreas RosenwaldKatja MaurusMDPI AGarticlemycosis fungoidescutaneous T-cell-lymphomapanel sequencinglarge cell transformationCD30Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5512, p 5512 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mycosis fungoides cutaneous T-cell-lymphoma panel sequencing large cell transformation CD30 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mycosis fungoides cutaneous T-cell-lymphoma panel sequencing large cell transformation CD30 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Marion Wobser Sabine Roth Silke Appenzeller Roland Houben David Schrama Matthias Goebeler Eva Geissinger Andreas Rosenwald Katja Maurus Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
description	Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). The analyzed patients were attributed to three different groups based on the presence of LCT and clinical behavior. Results: While indolent MF cases without LCT did not show pathogenic driver mutations, a high rate of oncogenic alterations was detected in patients with LCT and aggressive clinical courses. Various genes of different oncogenic signaling pathways, including the MAPK and JAK-STAT signaling pathways, as well as epigenetic modifiers were affected. A high inter-individual and distinctive intra-individual mutation diversity was observed. Oncogenic RAS mutations were exclusively detected in patients with LCT. Conclusion: Our data demonstrate that LCT transition of MF is associated with increased frequency of somatic mutations in cancer-associated genes. In particular, the activation of RAS signaling—together with epigenetic dysregulation—may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior.
format	article
author	Marion Wobser Sabine Roth Silke Appenzeller Roland Houben David Schrama Matthias Goebeler Eva Geissinger Andreas Rosenwald Katja Maurus
author_facet	Marion Wobser Sabine Roth Silke Appenzeller Roland Houben David Schrama Matthias Goebeler Eva Geissinger Andreas Rosenwald Katja Maurus
author_sort	Marion Wobser
title	Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
title_short	Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
title_full	Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
title_fullStr	Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
title_full_unstemmed	Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation
title_sort	targeted deep sequencing of mycosis fungoides reveals intracellular signaling pathways associated with aggressiveness and large cell transformation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/15afe10b47fb451e98654f4fce88d87d
work_keys_str_mv	AT marionwobser targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT sabineroth targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT silkeappenzeller targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT rolandhouben targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT davidschrama targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT matthiasgoebeler targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT evageissinger targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT andreasrosenwald targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation AT katjamaurus targeteddeepsequencingofmycosisfungoidesrevealsintracellularsignalingpathwaysassociatedwithaggressivenessandlargecelltransformation
_version_	1718435162496172032

Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation

Ejemplares similares