Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?

Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-reso...

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Autores principales:	Cristina L Ronchi, Silviu Sbiera, Ellen Leich, Katharina Henzel, Andreas Rosenwald, Bruno Allolio, Martin Fassnacht
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b21dc2260214f08b8ae88c3dd57bea6
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spelling	oai:doaj.org-article:1b21dc2260214f08b8ae88c3dd57bea62021-11-18T08:55:09ZSingle nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?1932-620310.1371/journal.pone.0073959https://doaj.org/article/1b21dc2260214f08b8ae88c3dd57bea62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24066089/?tool=EBIhttps://doaj.org/toc/1932-6203Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70% of gains frequent in benign were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.Cristina L RonchiSilviu SbieraEllen LeichKatharina HenzelAndreas RosenwaldBruno AllolioMartin FassnachtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73959 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cristina L Ronchi Silviu Sbiera Ellen Leich Katharina Henzel Andreas Rosenwald Bruno Allolio Martin Fassnacht Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
description	Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70% of gains frequent in benign were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.
format	article
author	Cristina L Ronchi Silviu Sbiera Ellen Leich Katharina Henzel Andreas Rosenwald Bruno Allolio Martin Fassnacht
author_facet	Cristina L Ronchi Silviu Sbiera Ellen Leich Katharina Henzel Andreas Rosenwald Bruno Allolio Martin Fassnacht
author_sort	Cristina L Ronchi
title	Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
title_short	Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
title_full	Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
title_fullStr	Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
title_full_unstemmed	Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
title_sort	single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1b21dc2260214f08b8ae88c3dd57bea6
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Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?

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