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31 October 2002, Volume 21, Number 50, Pages 7749-7763
Table of contents    Previous  Abstract  Next   Full text  PDF
Oncogenomics
Expression profiling of primary non-small cell lung cancer for target identification
Jim Heighway1, Teresa Knapp1, Lenetta Boyce1, Shelley Brennand1, John K Field1, Daniel C Betticher2, Daniel Ratschiller2, Mathias Gugger2, Michael Donovan3, Amy Lasek3 and Paula Rickert3

1Target Identification Group, Roy Castle International Centre for Lung Cancer Research, University of Liverpool, 200 London Road, Liverpool L3 9TA, UK

2Institute of Medical Oncology, University of Bern, 3010 Bern, Switzerland

3Incyte Genomics Inc., 3160 Porter Drive, Palo Alto, California, CA 94304, USA

Correspondence to: J Heighway or Paula Rickert, Gene Function, Roy Castle International Centre for Lung Cancer Research, 200 London Road, Liverpool L3 9TA, UK; E-mail: heighwayj@roycastle.liv.ac.uk or Paula Rickert, Incyte Genomics, 3160 Porter Drive, Palo Alto, California, CA 94304, USA; E-mail: prickert@incyte.com

Abstract

Using a panel of cDNA microarrays comprising 47 650 transcript elements, we have carried out a dual-channel analysis of gene expression in 39 resected primary human non-small cell lung tumours versus normal lung tissue. Whilst ~11 000 elements were scored as differentially expressed at least twofold in at least one sample, 96 transcripts were scored as over-represented fourfold or more in at least seven out of 39 tumours and 30 sequences 16-fold in at least two out of 39 tumours, including 24 transcripts in common. Transcripts (178) were found under-represented fourfold in at least seven out of 39 tumours, 31 of which are under-represented 16-fold in at least two out of 39 lesions. The relative expression levels of representative genes from these lists were analysed by comparative multiplex RT-PCR and found to be broadly consistent with the microarray data. Two dramatically over-represented genes, previously designated as potential tumour suppressors in breast (maspin) and lung and breast (S100A2) cancers, were analysed more extensively and demonstrate the effectiveness of this approach in identifying potential lung cancer diagnostic or therapeutic targets. Whilst it has been reported that S100A2 is downregulated in NSCLC at an early stage, our microarray, cmRT-PCR, Western and immunohistochemistry data indicate that it is strongly expressed in the majority of tumours.

Oncogene (2002) 21, 7749-7763. doi:10.1038/sj.onc.1205979

Keywords

lung; cancer; microarray; expression; target identification

Received 27 May 2002; revised 8 August 2002; accepted 13 August 2002
31 October 2002, Volume 21, Number 50, Pages 7749-7763
Table of contents    Previous  Abstract  Next   Full text  PDF
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