<p>Small cell lung cancer (SCLC) is among the most aggressive tumors with poor clinical outcomes. Tumors are rarely resected, which is a major barrier to molecular profiling of tumor tissue; therefore, non-invasive approaches using circulating tumor DNA (ctDNA) from liquid biopsies are needed to help advance research and clinical care for patients with SCLC. We developed a targeted capture panel that profiles SCLC genes and transcriptional regulation sites, including transcription start sites (TSS) and transcription factor binding sites (TFBS). This is a single assay that detects genomic mutations and transcriptional regulation activity based on ctDNA fragment patterns reflecting epigenetic nucleosomal positions. We applied this assay to sequence patient-derived xenograft (PDX) and patient plasma samples. We also performed whole genome sequencing (WGS) for a subset of the PDX plasma samples to validate the capture data. We developed new algorithms to quantify activity of key SCLC marker genes of <a href="https://www.ncbi.nlm.nih.gov/gene/429">ASCL1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/4760">NEUROD1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/25833">POU2F3</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/474">ATOH1</a> and to classify SCLC subtypes based on activity of these markers. Furthermore, we developed a model to classify SCLC from non-small cell lung cancer (NSCLC), which has potential important applications for monitoring transdifferentiation and tumor plasticity.</p>

Detecting and Subtyping Lung Cancer Through Analysis of Circulating Tumor    DNA

1 selected publication including "Molecular phenotyping of small cell lung cancer using targeted cfDNA p..." (22 citations)

Detecting and Subtyping Lung Cancer Through Analysis of Circulating Tumor DNA

Molecular phenotyping of small cell lung cancer using targeted cfDNA profiling of transcriptional regulatory regions