750: Molecular Sub-Classification of Kidney Tumors by CDNA Microarray and the Discovery of New Diagnostic Markers
Year: 2004
Type: conference-abstract
Abstract: diagnosis.This tumor occurs exclusively in young patients with sickle cell trait or disease.To date, very little is known about the underlying molecular basis, nor is there effective treatment for patients with this tumor.METHODS: We analyzed the gene expression profiles of two renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 eDNA clones and compared it to the gene expression profiles of 27 renal tumors including 7 clear cell renal cell carcinomas (RCC), 6 papillary RCC, 6 chromophobe RCC, 5 Wilms tumors, and 3 urothelial carcinomas of the renal pelvis.Comparative Genomic Microarray Analysis (CGMA), a recently developed method to identify chromosomal loss or gain based on overall gene expression patterns, was then performed.A heat map of a given chromosomal arm was created for each tumor.Two renal medullary carcinomas were compared wtih 9 clear cell RCC and 5 papillary RCC.Immunohistochemistry was performed using monoclonal antibodies specific for DNA topoisomerase IIa (Topo IIa) and keration 19 respectively.RESULTS: We found a distinct molecular signature of renal medullary carcinoma and closer clustering with urothelial carcinoma of the renal pelvis than conventional renal cell carcinoma, based on global gene clustering with 3,560 selected cDNAs.Noticeably, overexpression ofTopo IIa, which has been reported in Wilms tumors but not any other renal tumors, was significantly increased.Keratin 19, which has been previously found in urothelial carcinoma, was also overexpressed in renal medullary carcinomas.With CGMA, renal medullary carcinomas did not demonstrate any significant chromosomal gain or loss, in contrast to clear cell RCC with a characteristic loss of chromosome 3p (VHL) and papillary RCC with gains of chromosomes 7, 16, and 17.The overexpression of Topo IIa and keratin 19 in renal medullary carcinoma cells was confirmed by immunohistochemistry.CONCLUSIONS: Gene expression profiling shows a distinct molecular signature of renal medullary carcinoma, and close clustering with urothelial carcinoma.The genes specifically expressed in this tumor could lead to not only a better understanding of its molecular pathways, but also discoveries of potential diagnostic markers and therapeutic targets.
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2791165342