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Series GSE23644 Query DataSets for GSE23644
Status Public on Aug 02, 2011
Title DNA copy number alterations in endobronchial squamous metaplastic lesions predict lung cancer
Organism Homo sapiens
Experiment type Genome variation profiling by array
Summary BACKGROUND
Autofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions. Our present study was set out to identify AFB-visualized squamous metaplastic lesions with malignant potential by DNA copy number profiling.

METHODS
Regular AFB-examinations in 474 subjects at risk of lung cancer identified 6 subjects with SqM lesions at baseline and carcinoma (in situ) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and arrayCGH-based chromosomal profiles to 23 SqM of subjects who remained cancer-free. Specific copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined.

RESULTS
At baseline, p53, p63 and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared to controls (p<0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (FWER<0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased towards cancer progression. CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, predicted cancer risk for AFB-visualized SqM with 97% accuracy.

CONCLUSION
Our data strongly suggest that the presence of specific DNA copy number alterations in endobronchial SqM lesions predict endobronchial cancer.
 
Overall design Fresh frozen specimens of 29 squamous metaplastic AFB-visualized baseline biopsies, 23 location-matched follow-up biopsies, 6 biopsies of anatomically distinct sites of 4 cases. Test samples were compared to an external pool of normal male/female reference DNA.
 
Contributor(s) van Boerdonk RA, Sutedja TG, Snijders PJ, Reinen E, Wilting SM, van de Wiel MA, Thunnissen FB, Duin S, Kooi C, Ylstra B, Meijer CJ, Meijer GA, Daniëls JM, Postmus PE, Smit EF, Heideman DA
Citation(s) 21799074
Submission date Aug 16, 2010
Last update date Jun 20, 2013
Contact name Daoud Sie
E-mail(s) [email protected]
Phone +31 20 4442428
Organization name Vrije Universiteit Medical Center
Department Pathology
Lab Microarray Core Facility
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
 
Platforms (1)
GPL8841 Agilent-014950 Human Genome CGH Microarray 4x44K (Probe Name version)
Samples (58)
GSM580047 Case 02 baseline Squamous Metaplasia
GSM580048 Case 03 baseline Squamous Metaplasia
GSM580049 Case 04 baseline Squamous Metaplasia
Relations
BioProject PRJNA130957

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE23644_RAW.tar 1.6 Gb (http)(custom) TAR (of TXT)
Processed data included within Sample table
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