Lung_Progression_versus_Regression_Whole_Genome_Sequencing

Around 50 samples of pre-invasive lung cancer lesions showing subsequent clinical and pathological progression or regression

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001001271	Around 50 samples of pre-invasive lung cancer lesions showing subsequent clinical and pathological progression or regression	HiSeq X Ten	50
EGAD00001003883	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.	HiSeq X Ten	69

Publications	Citations
Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Teixeira VH, Pipinikas CP, Pennycuick A, Lee-Six H, Chandrasekharan D, Beane J, Morris TJ, Karpathakis A, Feber A, Breeze CE, Ntolios P, Hynds RE, Falzon M, Capitanio A, Carroll B, Durrenberger PF, Hardavella G, Brown JM, Lynch AG, Farmery H, Paul DS, Chambers RC, McGranahan N, Navani N, Thakrar RM, Swanton C, Beck S, George PJ, Spira A, Campbell PJ, Thirlwell C, Janes SM. Nat Med 25: 2019 517-525	132
Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer. Pennycuick A, Teixeira VH, AbdulJabbar K, Raza SEA, Lund T, Akarca AU, Rosenthal R, Kalinke L, Chandrasekharan DP, Pipinikas CP, Lee-Six H, Hynds RE, Gowers KHC, Henry JY, Millar FR, Hagos YB, Denais C, Falzon M, Moore DA, Antoniou S, Durrenberger PF, Furness AJ, Carroll B, Marceaux C, Asselin-Labat ML, Larson W, Betts C, Coussens LM, Thakrar RM, George J, Swanton C, Thirlwell C, Campbell PJ, Marafioti T, Yuan Y, Quezada SA, McGranahan N, Janes SM. Cancer Discov 10: 2020 1489-1499	50

Publications

Citations

Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.
Teixeira VH, Pipinikas CP, Pennycuick A, Lee-Six H, Chandrasekharan D, Beane J, Morris TJ, Karpathakis A, Feber A, Breeze CE, Ntolios P, Hynds RE, Falzon M, Capitanio A, Carroll B, Durrenberger PF, Hardavella G, Brown JM, Lynch AG, Farmery H, Paul DS, Chambers RC, McGranahan N, Navani N, Thakrar RM, Swanton C, Beck S, George PJ, Spira A, Campbell PJ, Thirlwell C, Janes SM. Nat Med 25: 2019 517-525

132

Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.
Pennycuick A, Teixeira VH, AbdulJabbar K, Raza SEA, Lund T, Akarca AU, Rosenthal R, Kalinke L, Chandrasekharan DP, Pipinikas CP, Lee-Six H, Hynds RE, Gowers KHC, Henry JY, Millar FR, Hagos YB, Denais C, Falzon M, Moore DA, Antoniou S, Durrenberger PF, Furness AJ, Carroll B, Marceaux C, Asselin-Labat ML, Larson W, Betts C, Coussens LM, Thakrar RM, George J, Swanton C, Thirlwell C, Campbell PJ, Marafioti T, Yuan Y, Quezada SA, McGranahan N, Janes SM. Cancer Discov 10: 2020 1489-1499