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| Status |
Public on Jul 01, 2005 |
| Title |
A molecular classification of papillary renal cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND: Despite the moderate incidence of papillary renal cell carcinoma
(PRCC), there is a disproportionately limited understanding of its underlying genetic
programs. There is no effective therapy for metastatic PRCC, and patients are often
excluded from kidney cancer trials. A morphological classification of PRCC into Type 1 and Type 2 tumors has been recently proposed, but its biological relevance remains uncertain.
PATIENTS AND METHODS. We studied the gene expression profiles of 34 cases of
PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both
unsupervised and supervised analysis. Comparative genomic microarray analysis
(CGMA) was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples, with 15 independent tumors.
RESULTS. We identified 2 highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to 3 histological subtypes: Type 1, low-grade Type 2 and mixed Type 1/low-grade Type 2 tumors. The second class, with poor survival, corresponded to high-grade Type 2 tumors
(n=11). Dysregulation of G1/S and G2/M checkpoint genes were found in Class 1 and
Class 2 tumors respectively, alongside characteristic chromosomal aberrations. We
identified a 7-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in Class 1 tumors, and of topoisomerase IIα in Class 2 tumors.
CONCLUSIONS. We report 2 molecular subclasses of PRCC, which are biologically
and clinically distinct, which may be readily distinguished in a clinical setting.
Keywords: survival, prognostic classification, disease state analysis
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| Overall design |
34 individual samples analyzed, no technical replicates.
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| Contributor(s) |
Tan M, Teh B |
| Citation(s) |
15994935 |
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| Submission date |
Jun 04, 2005 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Min-Han Tan |
| Organization name |
Van Andel Research Institute
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| Lab |
Cancer Genetics
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| Street address |
333 Bostwick Ave NE
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| City |
Grand Rapids |
| State/province |
MI |
| ZIP/Postal code |
49503 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (34)
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| Relations |
| BioProject |
PRJNA92221 |
| Supplementary data files not provided |
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