E-GEOD-45287 - DNA copy number profiles of premalignant endobronchial lesions: a validated predictor for endobronchial cancer
Released on 3 December 2013, last updated on 2 June 2014
Individuals who present with premalignant endobronchial lesions are considered at high risk of lung cancer. Nonetheless, premalignant lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer to better tailor treatment choices and avoid unnecessary follow-up procedures. We recently proposed a classifier of DNA copy number alterations (CNAs) at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 as risk predictor for endobronchial cancer. The current study was set out to validate the classifier among an independent series of premalignant endobronchial lesions with various histological grades. A series of 36 endobronchial premalignant lesions (8 squamous metaplasia, and 28 various grades of dysplasia) identified during autofluorescence bronchoscopy of 12 case subjects who had carcinoma in situ or carcinoma (≥CIS) during follow-up bronchoscopy at the initial site and 24 control subjects who remained cancer-free, was subjected to array Comparative Genomic Hybridization (arrayCGH). DNA copy number profiles were related to lesion outcome. Prediction accuracy of the previously defined molecular classifier to predict endobronchial cancer in this series was determined. Unsupervised hierarchical clustering analysis revealed a significant association between cluster assignment and lesion outcome (p< 0.001), independent of histological grade, with quiescent profiles in controls (24/24) and aberrant profiles in the majority of cases (9/12). Our pre-defined classifier demonstrated 92% accuracy for predicting cancer outcome in the current sample series. Our validated classifier holds great promise for stratification of patients with premalignant endobronchial lesions for risk of subsequent cancer. Fresh frozen specimens of 36 premalignant endobronchial biopsies. Test samples were compared to an external pool of normal male/female reference DNA.
comparative genomic hybridization by array
Daoud Sie <email@example.com>, Bauke Ylstra, Daniëlle A Heideman, Egbert F Smit, Erik Thunnissen, Gerrit A Meijer, Johannes M Daniels, Katrien Grünberg, Mark A van de Wiel, Peter J Snijders, Pieter E Postmus, Robert A van Boerdonk, Thomas G Sutedja
DNA copy number aberrations in endobronchial lesions: a validated predictor for cancer. van Boerdonk RA, Daniels JM, Snijders PJ, Grï¿½nberg K, Thunnissen E, van de Wiel MA, Ylstra B, Postmus PE, Meijer CJ, Meijer GA, Smit EF, Sutedja TG, Heideman DA. , Europe PMC 24227199