The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas

International Journal of Molecular Sciences

Gerardo Guinto¹  Jorge T. Ayala-Sumuano²  Lesly A. Portocarrero-Ortiz³  Sergio Moreno-Jimenez³  Javier Gaytan-Cervantes⁴  Carolina Gonzalez-Torres⁴  Blas Lopez-Felix⁵  Keiko Taniguchi-Ponciano⁶  Gloria Silva-Román⁶  Lourdes Basurto-Acevedo⁶  Andres Burak-Leipuner⁶  Ana-Laura Espinosa-de-los-Monteros⁶  Sandra Vela-Patiño⁶  Moisés Mercado⁶  Daniel Marrero-Rodríguez⁶  Eduardo Peña-Martínez⁶  Renata Saucedo⁶  Sergio Andonegui-Elguera⁶  Ilan Remba-Shapiro⁶  Laura Chavez-Macias⁷  Erick Gómez-Apo⁷ 

[1] Centro Neurológico, Centro Medico ABC, Ciudad de Mexico 01120, Mexico;IDIX Biotech, Queretaro 76235, Mexico;Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”, Ciudad de Mexico 14269, Mexico;Laboratorio de Secuenciacion, Division de Desarrollo de la Investigacion, Centro Medico Nacional Siglo XXI, Ciudad de Mexico 06720, Mexico;Servicio de Neurocirugía, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico 06720, Mexico;Unidad de Investigación Medica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico 06720, Mexico;Área de Neuropatología, Servicio de Anatomía Patológica, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de Mexico 06720, Mexico;

关键词: corticotroph;    Cushing disease;    ACTH-secreting carcinoma;    single nucleotide variation;    copy number variation;    exome;   

DOI  :  10.3390/ijms23094861

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown