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Title: A molecular classification of papillary renal cell carcinoma
Authors: Yang, X.J
Tan, M.-H 
Kim, H.L
Ditlev, J.A
Betten, M.W
Png, C.E
Kort, E.J
Futami, K
Furge, K.A
Takahashi, M
Kanayama, H.-O
Tan, P.H
Teh, B.S
Luan, C
Wang, K
Pins, M
Tretiakova, M
Anema, J
Kahnoski, R
Nicol, T
Stadler, W
Vogelzang, N.G
Amato, R
Seligson, D
Figlin, R
Belldegrun, A
Rogers, C.G
Teh, B.T 
Keywords: cytokeratin 7
DNA topoisomerase (ATP hydrolysing) A
cancer classification
cell cycle G2 phase
cell cycle S phase
chromosome aberration
clinical article
comparative genomic hybridization
gene expression profiling
gene expression regulation
genetic analysis
genetic selection
kidney carcinoma
molecular genetics
papillary carcinoma
priority journal
Carcinoma, Papillary
Carcinoma, Renal Cell
Chromosome Aberrations
Gene Expression Profiling
Kidney Neoplasms
Middle Aged
Oligonucleotide Array Sequence Analysis
Issue Date: 2005
Citation: Yang, X.J, Tan, M.-H, Kim, H.L, Ditlev, J.A, Betten, M.W, Png, C.E, Kort, E.J, Futami, K, Furge, K.A, Takahashi, M, Kanayama, H.-O, Tan, P.H, Teh, B.S, Luan, C, Wang, K, Pins, M, Tretiakova, M, Anema, J, Kahnoski, R, Nicol, T, Stadler, W, Vogelzang, N.G, Amato, R, Seligson, D, Figlin, R, Belldegrun, A, Rogers, C.G, Teh, B.T (2005). A molecular classification of papillary renal cell carcinoma. Cancer Research 65 (13) : 5628-5637. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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 morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. 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 analyses. Comparative genomic microarray analysis 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. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic 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 G 1-S and G 2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-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 II? in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting. ©2005 American Association for Cancer Research.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-05-0533
Rights: Attribution 4.0 International
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