In an article published on 21 January 2019 in the Nature Medicine, Sam M. Janes of the University College London in London, UK and colleagues described the genomic, transcriptomic, and epigenomic landscape of lung carcinoma in situ (CIS) in a unique patient cohort with longitudinally monitored pre-invasive disease.
The authors wrote that the molecular alterations that occur in cells before lung cancer is manifested are largely uncharted. Lung CIS lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of such clinical observation is unknown which prompted the researchers to perform the latest study.
Predictive modelling identified which lesions will progress with remarkable accuracy. In particular, the investigators identified progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. They observed mutations and copy number changes characteristic of cancer and charted their emergence, offering a window into early carcinogenesis.
The study team anticipate that this new understanding of cancer precursor biology may improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.
The published results are in part based on data generated by a TCGA pilot project established by the National Cancer Institute and National Human Genome Research Institute. Four authors are supported by the Wellcome Trust fellowships. The lead author is also supported by the Rosetrees Trust, the Welton Trust, the Garfield Weston Trust, the Stoneygate Trust and UCLH Charitable Foundation. Three authors have been funded by the Roy Castle Lung Cancer Foundation. In addition, one author is funded by a Wellcome Trust clinical PhD training fellowship and one by the Wellcome Trust Sanger Institute non-clinical PhD studentship. This work was partially undertaken at University College London Hospital/ University College London, who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme. Four authors are part of the CRUK Lung Cancer Centre of Excellence and three are supported by Stand Up to Cancer.
The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Discoveries within the manuscript have led Sam M. Janes to lead on Patent Applications 1819453.0 and 1819452.2 filed with the UK Intellectual Property Office through UCL Business PLC.
Teixeira VH, Pipinikas CP, Pennycuick A, et al. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nature Medicine; Published online 21 January 2019. doi: 10.1038/s41591-018-0323-0.