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The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas
Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poor...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106092/ https://www.ncbi.nlm.nih.gov/pubmed/35563252 http://dx.doi.org/10.3390/ijms23094861 |
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author | Andonegui-Elguera, Sergio Silva-Román, Gloria Peña-Martínez, Eduardo Taniguchi-Ponciano, Keiko Vela-Patiño, Sandra Remba-Shapiro, Ilan Gómez-Apo, Erick Espinosa-de-los-Monteros, Ana-Laura Portocarrero-Ortiz, Lesly A. Guinto, Gerardo Moreno-Jimenez, Sergio Chavez-Macias, Laura Saucedo, Renata Basurto-Acevedo, Lourdes Lopez-Felix, Blas Gonzalez-Torres, Carolina Gaytan-Cervantes, Javier Ayala-Sumuano, Jorge T. Burak-Leipuner, Andres Marrero-Rodríguez, Daniel Mercado, Moisés |
author_facet | Andonegui-Elguera, Sergio Silva-Román, Gloria Peña-Martínez, Eduardo Taniguchi-Ponciano, Keiko Vela-Patiño, Sandra Remba-Shapiro, Ilan Gómez-Apo, Erick Espinosa-de-los-Monteros, Ana-Laura Portocarrero-Ortiz, Lesly A. Guinto, Gerardo Moreno-Jimenez, Sergio Chavez-Macias, Laura Saucedo, Renata Basurto-Acevedo, Lourdes Lopez-Felix, Blas Gonzalez-Torres, Carolina Gaytan-Cervantes, Javier Ayala-Sumuano, Jorge T. Burak-Leipuner, Andres Marrero-Rodríguez, Daniel Mercado, Moisés |
author_sort | Andonegui-Elguera, Sergio |
collection | PubMed |
description | Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors. |
format | Online Article Text |
id | pubmed-9106092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91060922022-05-14 The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas Andonegui-Elguera, Sergio Silva-Román, Gloria Peña-Martínez, Eduardo Taniguchi-Ponciano, Keiko Vela-Patiño, Sandra Remba-Shapiro, Ilan Gómez-Apo, Erick Espinosa-de-los-Monteros, Ana-Laura Portocarrero-Ortiz, Lesly A. Guinto, Gerardo Moreno-Jimenez, Sergio Chavez-Macias, Laura Saucedo, Renata Basurto-Acevedo, Lourdes Lopez-Felix, Blas Gonzalez-Torres, Carolina Gaytan-Cervantes, Javier Ayala-Sumuano, Jorge T. Burak-Leipuner, Andres Marrero-Rodríguez, Daniel Mercado, Moisés Int J Mol Sci Article Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors. MDPI 2022-04-27 /pmc/articles/PMC9106092/ /pubmed/35563252 http://dx.doi.org/10.3390/ijms23094861 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Andonegui-Elguera, Sergio Silva-Román, Gloria Peña-Martínez, Eduardo Taniguchi-Ponciano, Keiko Vela-Patiño, Sandra Remba-Shapiro, Ilan Gómez-Apo, Erick Espinosa-de-los-Monteros, Ana-Laura Portocarrero-Ortiz, Lesly A. Guinto, Gerardo Moreno-Jimenez, Sergio Chavez-Macias, Laura Saucedo, Renata Basurto-Acevedo, Lourdes Lopez-Felix, Blas Gonzalez-Torres, Carolina Gaytan-Cervantes, Javier Ayala-Sumuano, Jorge T. Burak-Leipuner, Andres Marrero-Rodríguez, Daniel Mercado, Moisés The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title | The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title_full | The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title_fullStr | The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title_full_unstemmed | The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title_short | The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas |
title_sort | genomic landscape of corticotroph tumors: from silent adenomas to acth-secreting carcinomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106092/ https://www.ncbi.nlm.nih.gov/pubmed/35563252 http://dx.doi.org/10.3390/ijms23094861 |
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