Detection of early-stage lung cancers via tumor DNA in blood

It is widely acknowledged that improvements in non-invasive strategies for early detection of lung cancer are likely to translate to substantial reductions in cancer-related deaths. Efforts to develop blood tests for this purpose have largely focused on protein biomarkers, but it has been challenging to identify proteins that are sufficiently cancer-specific. The recent emergence of next-generation, high-throughput DNA sequencing technologies has made it possible to detect and quantify very small quantities of tumor-derived DNA in a patient’s bloodstream. Because such circulating tumor DNA can be identified based on the presence of mutations that are exquisitely tumor-specific and should rarely be found in healthy individuals, it holds promise as a biomarker for cancer screening. This laboratory has developed an ultrasensitive method to measure mutated tumor-derived DNA fragments in blood. By applying novel error-suppression techniques to high-throughput sequence data, they are able to identify and quantify low-abundance mutations within a broad panel of genes that are commonly mutated in lung cancer. To evaluate the potential clinical utility of this approach for lung cancer screening, blood samples obtained from patients with small, early-stage lung tumors will be tested. Samples obtained from individuals with a heavy smoking history and individuals with benign pulmonary nodules will then be compared. If the test performs well at identifying patients with lung cancer with few false-positive results, larger-scale clinical studies for screening of high-risk patients will then be justified.