PMID- 14871811
OWN - NLM
STAT- MEDLINE
DCOM- 20040409
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 3
DP  - 2004 Feb 1
TI  - Tissue-wide expression profiling using cDNA subtraction and microarrays to 
      identify tumor-specific genes.
PG  - 844-56
AB  - With the objective of discovering novel putative intervention sites for 
      anticancer therapy, we compared transcriptional profiles of breast cancer, lung 
      squamous cell cancer (LSCC), lung adenocarcinoma (LAC), and renal cell cancer 
      (RCC). Each of these tumor types still needs improvement in medical treatment. 
      Our intention was to search for genes not only highly expressed in the majority 
      of patient samples but which also exhibit very low or even absence of expression 
      in a comprehensive panel of 16 critical (vital) normal tissues. To achieve this 
      goal, we combined two powerful technologies, PCR-based cDNA subtraction and cDNA 
      microarrays. Seven subtractive libraries consisting of approximately 9250 clones 
      were established and enriched for tumor-specific transcripts. These clones, 
      together with approximately 1750 additional tumor-relevant genes, were used for 
      cDNA microarray preparation. Hybridizations were performed using a pool of 16 
      critical normal tissues as a reference in all experiments. In total, we analyzed 
      20 samples of breast cancer, 11 of LSCC, 11 of LAC, and 8 of RCC. To select for 
      genes with low or even no expression in normal tissues, expression profiles of 22 
      different normal tissues were additionally analyzed. Importantly, this 
      tissue-wide expression profiling allowed us to eliminate genes, which exhibit 
      also high expression in normal tissues. Similarly, expression signatures of 
      genes, which are derived from infiltrating cells of the immune system, were 
      eliminated as well. Cluster analysis resulted in the identification of 527 
      expressed sequence tags specifically up-regulated in these tumors. Gene-wise 
      hierarchical clustering of these clones clearly separated the different tumor 
      types with RCC exhibiting the most homogeneous and LAC the most diverse 
      expression profile. In addition to already known tumor-associated genes, the 
      majority of identified genes have not yet been brought into context with 
      tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and 
      OSF-2) in lung, breast, and kidney cancer or genes controlling Ca(2+) homeostasis 
      (RCN1,CALCA, S100 protein family). EGLN3, which recently has been shown to be 
      involved in regulation of hypoxia-inducible factor, was found to be highly 
      up-regulated in all RCCs and in half of the LSCCs analyzed. Furthermore, 42 
      genes, the expression level of which correlated with the overall survival of 
      breast cancer patients, were identified. The gene dendogram clearly separates two 
      groups of genes, those up-regulated such as cyclin B1, TGF-beta 3, B-Myb, Erg2, 
      VCAM-1, and CD44 and those down-regulated such as MIG-6, Esp15, and CAK in 
      patients with short survival time.
FAU - Amatschek, Stefan
AU  - Amatschek S
AD  - Department of Dermatology, University of Vienna, Vienna, Austria.
FAU - Koenig, Ulrich
AU  - Koenig U
FAU - Auer, Herbert
AU  - Auer H
FAU - Steinlein, Peter
AU  - Steinlein P
FAU - Pacher, Margit
AU  - Pacher M
FAU - Gruenfelder, Agnes
AU  - Gruenfelder A
FAU - Dekan, Gerhard
AU  - Dekan G
FAU - Vogl, Sonja
AU  - Vogl S
FAU - Kubista, Ernst
AU  - Kubista E
FAU - Heider, Karl-Heinz
AU  - Heider KH
FAU - Stratowa, Christian
AU  - Stratowa C
FAU - Schreiber, Martin
AU  - Schreiber M
FAU - Sommergruber, Wolfgang
AU  - Sommergruber W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (RNA, Neoplasm)
SB  - IM
MH  - Adenocarcinoma/*genetics/metabolism/pathology
MH  - Breast Neoplasms/*genetics/metabolism/pathology
MH  - Carcinoma, Renal Cell/*genetics/metabolism/pathology
MH  - Carcinoma, Squamous Cell/*genetics/metabolism/pathology
MH  - Cluster Analysis
MH  - Gene Expression Profiling
MH  - Humans
MH  - Kidney Neoplasms/*genetics/metabolism/pathology
MH  - Lung Neoplasms/*genetics/metabolism/pathology
MH  - Neoplasm Staging
MH  - Nucleic Acid Hybridization
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Neoplasm/genetics/isolation & purification
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Rate
EDAT- 2004/02/12 05:00
MHDA- 2004/04/10 05:00
CRDT- 2004/02/12 05:00
PHST- 2004/02/12 05:00 [pubmed]
PHST- 2004/04/10 05:00 [medline]
PHST- 2004/02/12 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-2361 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Feb 1;64(3):844-56. doi: 10.1158/0008-5472.can-03-2361.