Journal Article

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

Rappold, Gudrun, Liebenberg, Volker, Merk, Johannes, Weickmann, Sabine, Fleischhacker, Michael, Vossenaar, Erik R, Schmidt, Bernd, Erdogan, Fikret, Schneider, Katja U, Dietrich, Dimo, Leschber, Gunda, Kneip, Christoph, Seegebarth, Anke, Stapert, Henk R, Schäper, Frank

2011

Overview

Background DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. Methods SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. Results A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. Conclusions Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Biomarkers / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Biomarkers, Tumor - physiology / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma - diagnosis / Carcinoma - genetics / Carcinoma - metabolism / Carcinoma - pathology / Chromosomes / Comparative Genomic Hybridization / Deoxyribonucleic acid / Diagnosis / DNA / DNA methylation / DNA Methylation - physiology / DNA Mutational Analysis - methods / Epigenetics / Ethanol / Gene amplification / Gene Amplification - physiology / Gene Dosage - physiology / Gene expression / Genetic aspects / Genetic markers / Genetics / Genomes / genomics and epigenetics / Health Promotion and Disease Prevention / Homeobox genes / Homeodomain Proteins - genetics / Homeodomain Proteins - metabolism / Homeodomain Proteins - physiology / Homeotic genes / Humans / Identification and classification / Lung cancer / Lung diseases / Lung Neoplasms - diagnosis / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Matched-Pair Analysis / Medicine/Public Health / Methylation / Oncology / Physiological aspects / Polymorphism, Genetic / Research Article / Reverse Transcriptase Polymerase Chain Reaction / Studies / Surgical Oncology