Genomics

Dataset Information

20

DNA copy number alterations in endobronchial squamous metaplastic lesions predict lung cancer


ABSTRACT: 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.

INSTRUMENT(S): Agilent-014950 Human Genome CGH Microarray 4x44K (Probe Name version)

SUBMITTER: Daoud Sie   

PROVIDER: GSE23644 | GEO | 2011-08-02

SECONDARY ACCESSION(S): PRJNA130957

REPOSITORIES: GEO

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RATIONALE: 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. OBJECTIVES: The present study set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling. METHODS: Regular AFB examinations in 474 subjects at risk of lung cancer identified six subjects with SqM lesions  ...[more]

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