Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.

Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exc...

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Autores principales:	Sara Martoreli Silveira, Rolando Andre Rios Villacis, Fabio Albuquerque Marchi, Mateus de Camargo Barros Filho, Sandra Aparecida Drigo, Cristovam Scapulatempo Neto, Ademar Lopes, Isabela Werneck da Cunha, Silvia Regina Rogatto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/417612bdb08b4a4a83d91c3d2fbe58a0
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spelling	oai:doaj.org-article:417612bdb08b4a4a83d91c3d2fbe58a02021-11-18T07:40:02ZGenomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.1932-620310.1371/journal.pone.0067643https://doaj.org/article/417612bdb08b4a4a83d91c3d2fbe58a02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23825676/?tool=EBIhttps://doaj.org/toc/1932-6203Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exclusion is frequently used. In this study, array-based comparative genomic hybridization (array CGH) was used to analyze 20 UPS and 17 LMS samples from untreated patients. The LMS samples presented a lower frequency of genomic alterations compared with the UPS samples. The most frequently altered UPS regions involved gains at 20q13.33 and 7q22.1 and losses at 3p26.3. Gains at 8q24.3 and 19q13.12 and losses at 9p21.3 were frequently detected in the LMS samples. Of these regions, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 were significantly associated with reduced overall survival times in LMS patients. A multivariate analysis revealed that gains at 1q21.3 were an independent prognostic marker of shorter survival times in LMS patients (HR = 13.76; P = 0.019). Although the copy number profiles of the UPS and LMS samples could not be distinguished using unsupervised hierarchical clustering analysis, one of the three clusters presented cases associated with poor prognostic outcome (P = 0.022). A relative copy number analysis for the ARNT, SLC27A3, and PBXIP1 genes was performed using quantitative real-time PCR in 11 LMS and 16 UPS samples. Gains at 1q21-q22 were observed in both tumor types, particularly in the UPS samples. These findings provide strong evidence for the existence of a genomic signature to predict poor outcome in a subset of UPS and LMS patients.Sara Martoreli SilveiraRolando Andre Rios VillacisFabio Albuquerque MarchiMateus de Camargo Barros FilhoSandra Aparecida DrigoCristovam Scapulatempo NetoAdemar LopesIsabela Werneck da CunhaSilvia Regina RogattoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e67643 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Martoreli Silveira Rolando Andre Rios Villacis Fabio Albuquerque Marchi Mateus de Camargo Barros Filho Sandra Aparecida Drigo Cristovam Scapulatempo Neto Ademar Lopes Isabela Werneck da Cunha Silvia Regina Rogatto Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
description	Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exclusion is frequently used. In this study, array-based comparative genomic hybridization (array CGH) was used to analyze 20 UPS and 17 LMS samples from untreated patients. The LMS samples presented a lower frequency of genomic alterations compared with the UPS samples. The most frequently altered UPS regions involved gains at 20q13.33 and 7q22.1 and losses at 3p26.3. Gains at 8q24.3 and 19q13.12 and losses at 9p21.3 were frequently detected in the LMS samples. Of these regions, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 were significantly associated with reduced overall survival times in LMS patients. A multivariate analysis revealed that gains at 1q21.3 were an independent prognostic marker of shorter survival times in LMS patients (HR = 13.76; P = 0.019). Although the copy number profiles of the UPS and LMS samples could not be distinguished using unsupervised hierarchical clustering analysis, one of the three clusters presented cases associated with poor prognostic outcome (P = 0.022). A relative copy number analysis for the ARNT, SLC27A3, and PBXIP1 genes was performed using quantitative real-time PCR in 11 LMS and 16 UPS samples. Gains at 1q21-q22 were observed in both tumor types, particularly in the UPS samples. These findings provide strong evidence for the existence of a genomic signature to predict poor outcome in a subset of UPS and LMS patients.
format	article
author	Sara Martoreli Silveira Rolando Andre Rios Villacis Fabio Albuquerque Marchi Mateus de Camargo Barros Filho Sandra Aparecida Drigo Cristovam Scapulatempo Neto Ademar Lopes Isabela Werneck da Cunha Silvia Regina Rogatto
author_facet	Sara Martoreli Silveira Rolando Andre Rios Villacis Fabio Albuquerque Marchi Mateus de Camargo Barros Filho Sandra Aparecida Drigo Cristovam Scapulatempo Neto Ademar Lopes Isabela Werneck da Cunha Silvia Regina Rogatto
author_sort	Sara Martoreli Silveira
title	Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
title_short	Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
title_full	Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
title_fullStr	Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
title_full_unstemmed	Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
title_sort	genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/417612bdb08b4a4a83d91c3d2fbe58a0
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Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.

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