Predicting the Course of Lung Cancer in Situ
Posted: Tuesday, May 21, 2019
Data offering “the first insight into the molecular map of early lung squamous cancer pathogenesis” have been published in Nature Medicine. Potentially, this work may become the bedrock of full comprehension of the genes associated with chromosomal instability that determine why lung carcinoma in situ cells do or do not become squamous cell carcinoma.
Vitor H. Teixeira, PhD, MSc, of the University College London, United Kingdom, and colleagues analyzed the molecular alterations in an 85-patient/129-biopsy cohort with longitudinally monitored preinvasive disease. Lung carcinoma in situ cells, the authors described, are microscopically identical, but half of them progress to invasive cancer and half of them regress or remain static. After probing the genomic, transcriptomic, and epigenomic landscape of carcinoma in situ, the authors were able to devise a predictive modeling strategy to accurately identify which lesions will progress.
“We identif[ied] progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature,” explained the team. They found that instability—a high rate of gain or loss of whole or parts of chromosomes—was among the most reliable indicators associated with disease progression. Regressive lesions, Dr. Teixeira and colleagues continued, had much less genomic instability and more closely matched normal bronchial epithelium than invasive cancers.
“We observed mutations and copy number changes characteristic of cancer and chart[ed] their emergence, offering a window into early carcinogenesis,” they concluded. However, “international collaboration will be required to develop an appropriately powered trial” to allow the development of guidelines for treatment management decisions. The authors are confident, though, that eventually “molecular profiling will enable personally tailored therapeutic decisions for patients with preinvasive lung disease.”
Disclosure: The study authors’ disclosure information may be found at nature.com.
