Project description:Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, insertions and deletions. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.
Project description:Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Molecular profiling techniques have identified marked differences between progressive and regressive lesions. Here we present laser-captured stromal tissue, adjacent to previously profiled CIS lesions, to examine the role of the tumour microenvironment in spontaneous lesion regression. All samples in this dataset are paired with matched CIS lesions in dataset GSE108082.
Project description:Rationale: Lung carcinoma-in-situ (CIS) lesions are the pre-malignant precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those preinvasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. We performed gene expression microarrays on CIS lesions, with a view to deriving a molecular signature predictive of future progression to invasive cancer.
Project description:Rationale: Lung carcinoma-in-situ (CIS) lesions are the pre-malignant precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those preinvasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. We performed gene expression microarrays on CIS lesions, with a view to deriving a molecular signature predictive of future progression to invasive cancer.
Project description:Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, and copy number changes. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.
Project description:Colorectal adenomas are cancer precursor lesions of the large bowel. In these preinvasive lesions, a vast array of genomic and epigenomic changes have been detailed, but the consequence of these molecular alterations on the effectors of biological function (proteins) has not been comprehensively explored.
Project description:A low-grade invasive gastro-intestinal stromal tumour (GIST) was subjected to whole-genome sequencing as well as methylation profiling using Illumina 450K BeadChip array, in order to determine the minimal set of genomic and epigenomic alterations necessary to trigger the formation of invasive GIST. single-sample study, DNA extracted from fresh frozen tissue.
