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

被引:12
|
作者
Andonegui-Elguera, Sergio [1 ]
Silva-Roman, Gloria [1 ]
Pena-Martinez, Eduardo [1 ]
Taniguchi-Ponciano, Keiko [1 ]
Vela-Patino, Sandra [1 ]
Remba-Shapiro, Ilan [1 ]
Gomez-Apo, Erick [2 ]
Espinosa-de-los-Monteros, Ana-Laura [1 ]
Portocarrero-Ortiz, Lesly A. [3 ]
Guinto, Gerardo [4 ]
Moreno-Jimenez, Sergio [3 ,4 ]
Chavez-Macias, Laura [2 ,5 ]
Saucedo, Renata [1 ]
Basurto-Acevedo, Lourdes [1 ]
Lopez-Felix, Blas [6 ]
Gonzalez-Torres, Carolina [7 ]
Gaytan-Cervantes, Javier [7 ]
Ayala-Sumuano, Jorge T. [8 ]
Burak-Leipuner, Andres [1 ]
Marrero-Rodriguez, Daniel [1 ]
Mercado, Moises [1 ]
机构
[1] Inst Mexicano Seguro Social, Ctr Med Nacl Siglo XXI, Hosp Especialidades, Unidad Invest Med Enfermedades Endocrinas, Ciudad De Mexico 06720, Mexico
[2] Hosp Gen Mexico Dr Eduardo Liceaga, Serv Anat Patol, Area Neuropatol, Ciudad De Mexico 06720, Mexico
[3] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Ciudad De Mexico 14269, Mexico
[4] Ctr Med ABC, Ctr Neurol, Ciudad De Mexico 01120, Mexico
[5] Univ Nacl Autonoma Mexico, Fac Med, Ciudad De Mexico 04360, Mexico
[6] Inst Mexicano Seguro Social, Hosp Especialidades, Ctr Med Nacl Siglo XXI, Serv Neurocirugia, Ciudad De Mexico 06720, Mexico
[7] Ctr Med Nacl Siglo XXI, Div Desarrollo Invest, Lab Secuenciac, Ciudad De Mexico 06720, Mexico
[8] IDIX Biotech, Queretaro 76235, Mexico
关键词
corticotroph; Cushing disease; ACTH-secreting carcinoma; single nucleotide variation; copy number variation; exome; COPY NUMBER VARIATION; AGGRESSIVE PITUITARY-TUMORS; GENE POLYMORPHISMS; EUROPEAN-SOCIETY; USP8; MUTATIONS; EXPRESSION; DIAGNOSIS; GROWTH;
D O I
10.3390/ijms23094861
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
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页数:16
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