Genomic Signatures Predict Poor Outcome in Undifferentiated Pleomorphic Sarcomas and Leiomyosarcomas

Autor(es)

Silveira, Sara Martoreli ^[1] ; Rios Villacis, Rolando Andre ^[1] ; Marchi, Fabio Albuquerque ^[2] ; Barros Filho, Mateus de Camargo ^[1] ; Drigo, Sandra Aparecida ^[3] ; Neto, Cristovam Scapulatempo ^[4] ; Lopes, Ademar ^[5] ; da Cunha, Isabela Werneck ^[6] ; Rogatto, Silvia Regina ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Neogene Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Math & Stat, Interinst Program Bioinformat, BR-09500900 Sao Paulo - Brazil

^[3] Univ Estadual Paulista, Fac Med, Dept Urol, Sao Paulo - Brazil

^[4] Barretos Canc Hosp, Pio Fdn 12, Dept Pathol, Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Dept Pelv Surg, Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 6 JUN 25 2013.
• Citações Web of Science: 11

Resumo

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. (AU)

• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 08/55693-2 - Diagnostico molecular em sarcomas pleomorficos (fibrohistiocitoma maligno)
• Beneficiário: Sara Martoreli da Silveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado