Genomic Signatures Predict Poor Outcome in Undifferentiated Pleomorphic Sarcomas and Leiomyosarcomas

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorSilveira, Sara Martoreli
dc.creatorVillacis, Rolando Andre Rios
dc.creatorMarchi, Fabio Albuquerque
dc.creatorde Barros Filho, Mateus Camargo
dc.creatorLinde, Sandra Aparecida Drigo
dc.creatorNeto, Cristovam Scapulatempo
dc.creatorLopes, Ademar
dc.creatorda Cunha, Isabela Werneck
dc.creatorRogatto, Silvia Regina
dc.date2014-05-27T11:29:47Z
dc.date2016-10-25T18:50:10Z
dc.date2014-05-27T11:29:47Z
dc.date2016-10-25T18:50:10Z
dc.date2013-06-25
dc.date.accessioned2017-04-06T02:28:04Z
dc.date.available2017-04-06T02:28:04Z
dc.identifierPLoS ONE, v. 8, n. 6, 2013.
dc.identifier1932-6203
dc.identifierhttp://hdl.handle.net/11449/75707
dc.identifierhttp://acervodigital.unesp.br/handle/11449/75707
dc.identifier10.1371/journal.pone.0067643
dc.identifierWOS:000321223000112
dc.identifier2-s2.0-84879397016.pdf
dc.identifier2-s2.0-84879397016
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0067643
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/896443
dc.descriptionUndifferentiated 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. © 2013 Silveira et al.
dc.languageeng
dc.relationPLOS ONE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectantineoplastic agent
dc.subjectadjuvant therapy
dc.subjectadolescent
dc.subjectadult
dc.subjectaged
dc.subjectARNT gene
dc.subjectcancer prognosis
dc.subjectcancer radiotherapy
dc.subjectchild
dc.subjectchromosome 11q
dc.subjectchromosome 16p
dc.subjectchromosome 19q
dc.subjectchromosome 1q
dc.subjectchromosome 20q
dc.subjectchromosome 3p
dc.subjectchromosome 7q
dc.subjectchromosome 8q
dc.subjectchromosome 9p
dc.subjectchromosome loss
dc.subjectclinical article
dc.subjectcomparative genomic hybridization
dc.subjectfemale
dc.subjectgene
dc.subjectgene dosage
dc.subjectgene mutation
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectleiomyosarcoma
dc.subjectmale
dc.subjectmuscle resection
dc.subjectnucleotide sequence
dc.subjectoverall survival
dc.subjectPBXIP1 gene
dc.subjectpleomorphic sarcoma
dc.subjectprediction
dc.subjectpreschool child
dc.subjectquantitative analysis
dc.subjectreal time polymerase chain reaction
dc.subjectsarcoma
dc.subjectschool child
dc.subjectSLC27A3 gene
dc.titleGenomic Signatures Predict Poor Outcome in Undifferentiated Pleomorphic Sarcomas and Leiomyosarcomas
dc.typeOtro


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