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The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages

Authors :
Keiko Taniguchi-Ponciano
Lesly A. Portocarrero-Ortiz
Gerardo Guinto
Sergio Moreno-Jimenez
Erick Gomez-Apo
Laura Chavez-Macias
Eduardo Peña-Martínez
Gloria Silva-Román
Sandra Vela-Patiño
Jesús Ordoñez-García
Sergio Andonegui-Elguera
Aldo Ferreira-Hermosillo
Claudia Ramirez-Renteria
Etual Espinosa-Cardenas
Ernesto Sosa
Ana Laura Espinosa-de-los-Monteros
Latife Salame-Khouri
Carolina Perez
Blas Lopez-Felix
Guadalupe Vargas-Ortega
Baldomero Gonzalez-Virla
Marcos Lisbona-Buzali
Daniel Marrero-Rodríguez
Moisés Mercado
Source :
BMC Medical Genomics. 15
Publication Year :
2022
Publisher :
Springer Science and Business Media LLC, 2022.

Abstract

Background Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. Methods Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. Results The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. Conclusions The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Details

ISSN :
17558794
Volume :
15
Database :
OpenAIRE
Journal :
BMC Medical Genomics
Accession number :
edsair.doi.dedup.....5db8fd09ab3795479d8c2696845236da
Full Text :
https://doi.org/10.1186/s12920-022-01206-y