ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.

Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jenni Jaatinen, Tuukka Veija, Marko Salmikangas, Tom Böhling, Harri Sihto, Virve Koljonen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ba0b773467f4185a9e5fb91ca628588
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1ba0b773467f4185a9e5fb91ca628588
record_format	dspace
spelling	oai:doaj.org-article:1ba0b773467f4185a9e5fb91ca6285882021-12-02T20:11:14ZALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.1932-620310.1371/journal.pone.0252099https://doaj.org/article/1ba0b773467f4185a9e5fb91ca6285882021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252099https://doaj.org/toc/1932-6203Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.Jenni JaatinenTuukka VeijaMarko SalmikangasTom BöhlingHarri SihtoVirve KoljonenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252099 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenni Jaatinen Tuukka Veija Marko Salmikangas Tom Böhling Harri Sihto Virve Koljonen ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
description	Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.
format	article
author	Jenni Jaatinen Tuukka Veija Marko Salmikangas Tom Böhling Harri Sihto Virve Koljonen
author_facet	Jenni Jaatinen Tuukka Veija Marko Salmikangas Tom Böhling Harri Sihto Virve Koljonen
author_sort	Jenni Jaatinen
title	ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
title_short	ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
title_full	ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
title_fullStr	ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
title_full_unstemmed	ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.
title_sort	alk is frequently phosphorylated in merkel cell carcinoma and associates with longer survival.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1ba0b773467f4185a9e5fb91ca628588
work_keys_str_mv	AT jennijaatinen alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival AT tuukkaveija alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival AT markosalmikangas alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival AT tombohling alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival AT harrisihto alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival AT virvekoljonen alkisfrequentlyphosphorylatedinmerkelcellcarcinomaandassociateswithlongersurvival
_version_	1718374869436989440

ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.

Ejemplares similares