Expression profiles of metastasis-related genes in a cohort of childhood and adult adrenocortical tumors / Perfis de expressão de genes relacionados a metástases em uma coorte de pacientes adultos e pediátricos portadores de neoplasias do córtex da supra-renal
AUTOR(ES)
Antonio Marcondes Lerario
DATA DE PUBLICAÇÃO
2008
RESUMO
Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Although molecular studies have uncovered many aspects of ACC tumorigenesis, little is known about molecular pathways involved in metastatic spread. The objective of our study is to analyze the expression profile of metastasis-related genes in a cohort of metastatic and nonmetastatic adrenocortical tumors in order to identify genes involved in the metastatic spread, as well as to find new prognostic markers. The expression profiles of 27 adrenocortical tumors from 15 adults (8 ACC and 7 adenomas) and 12 children (5 metastatic and 7 non-metastatic) were evaluated by an array of 113 known to be involved in human metastasis. Cluster analysis showed adult adrenocortical adenomas form a group distinct from other adrenocortical tumors (adult carcinomas and pediatric tumors). The comparison of adult adenoma and ACC revealed that MMP11 and DENR were differentially expressed between these two groups while no gene was differentially expressed among pediatric adrenocortical tumors. Similarly to cluster analysis, Principal component analysis failed to identify partition amongst pediatric tumors categorized by their evolution. The expression data of MMP2, TIMP3 and FN1 genes by RT-PCR agreed with those generated by the arrays. LOH of 22q12.3 region was detected in some cases in which TIMP3 down regulation was verified (but not in all cases). In conclusion, we have identified important aspects of molecular pathways and biological characteristics involved in metastatic spread of adrenocortical tumors. Distinctive patterns of gene expression between metastatic and nonmetastatic tumors may help in prognosis prediction
ASSUNTO(S)
adrenal gland neoplasms/genetics neoplasias das glândulas supra-renais/genética análise de seqüência com séries de oligonucleotídeos adrenal gland neoplasms/diagnosis oligonucleotide array sequence analysis biological markers neoplasm metástases marcadores biológicos metástase neoplásica neoplasias das glândulas supra-renais/diagnóstico
