Increased concentrations of free-circulating plasma DNA (cpDNA) are observed in patients with invasive cancer, including lung cancer. Whether cpDNA levels are elevated in subjects with high-grade pre-invasive lesions of lung squamous cell carcinoma (SqCC) and whether its detection may be of value for identifying subjects at the highest risk of developing lung SqCC is currently unknown. The present study assessed cpDNA levels in subjects with high- and low-grade pre-invasive squamous endobronchial lesions relative to patients with clinically overt lung SqCC and healthy controls using real-time quantitative PCR methodology.
View Article and Find Full Text PDFBackground: PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors.
Design And Methods: The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols.
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.
To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes, and ectopic NKX2-1 or NKX2-2 expression for which rearrangements were identified.
View Article and Find Full Text PDFMethylation-mediated silencing of the tumour suppressor CADM1 has been functionally linked to lung cancer development. We aimed to determine whether CADM1 promoter methylation is a candidate early detection marker for lung cancer. To this end frozen tissue samples of 36 non-small cell lung cancers, 26 corresponding tumour distant normal tissue samples as well as 6 samples of normal lung from non-lung cancer patients were tested for DNA methylation at three different regions within the CADM1 promoter (M1, M5 and M9) using methylation specific PCR followed by methylation specific reverse line blot analysis.
View Article and Find Full Text PDFRationale: Bronchial epithelium exposed to cigarette smoke undergoes a series of histologic changes that may ultimately lead to invasive cancer. Inhaled corticosteroids reduce the number of lung tumors developing in rats exposed to cigarette smoke.
Objectives: We studied the effect of inhaled fluticasone on premalignant lesions in smokers and patients curatively treated for head and neck cancer or lung cancer.