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Molecular profiling could pick up lung cancer earlier

Genetic differences identified in precancerous lesions that progress to cancer could also lead to new treatments

Ingrid Torjesen

Wednesday, 23 January 2019

Researchers at University College London (UCL) have sequenced precancerous lung lesions for the first time and say the information generated, published in Nature Medicine*, could pave the way for very early detection of the disease and new treatments.

Before lung cancer develops, precancerous lesions are found in the airway, but only half of these will actually become lung cancer; others will disappear or remain benign without becoming harmful. Under the microscope, the lesions look the same, making it difficult to know which lesions to treat.

The sequencing by the UCL researchers highlights differences between the lesions that will become invasive and those that are harmless, enabling them to predict which lesions will become cancerous.

The researchers were studying biopsies of preinvasive lung cancer lesions of patients who were seen at University College London Hospital. They conducted tests including gene expression profiling, methylation profiling, and whole-genome DNA sequencing on 129 biopsy samples from 85 patients.

On average, the patients were followed up for over five years post-biopsy, to see which patients developed lung squamous cell carcinoma, one of the two most common subtypes of lung cancer.

The research team identified differences in genomic features such as mutations, gene expression and chromosomal instability, finding enough differences that they could predict with near-perfect accuracy which lesions would develop into cancer by checking the lesion's molecular profile.

By identifying which precancerous lesions are harmful, the researchers say clinicians could decide whether or not to offer a patient surgery at a much earlier stage of the disease than is currently possible, while saving others with benign lesions from unnecessary surgeries.

Precancerous lesions are detected by bronchoscopy, a minimally invasive test that is often done on people with chronic cough or a history of lung cancer. In some countries, patients with such lesions undergo surgery, while elsewhere, patients are monitored and only treated if clear signs of cancer appear.

While bronchoscopy isn't offered to everyone at risk of lung cancer, the researchers say their findings could help to develop a simpler blood test to pick up the same molecular signals that are linked to early cancer development.

"If we can use this new understanding of cancer development to create new diagnostic tests, it may one day be invaluable in picking up cancer early, enabling people to access treatment much earlier in the disease process," said one of the researchers, Dr Adam Pennycuick of UCL’s Division of Medicine.

The study could also help lead to new treatments, as some of the genes that are expressed differently in lesions that will become cancerous, have previously been identified as potential drivers of lung cancer.

*Teixeira VH, Pipinikas CP, Pennycuick A, et al. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.Nature Medicine (2019), 21 January, doi: 10.1038/s41591-018-0323-0

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