Joseph B Hiatt, Anna-Lisa Doebley, Henry U Arnold, Mohamed Adil, Holly Sandborg, Thomas W Persse, Minjeong Ko, Feinan Wu, Alvaro Quintanal Villalonga, Rafael Santana-Davila, Keith Eaton, Caroline Dive, Charles M Rudin, Anish Thomas, A McGarry Houghton, Gavin Ha, David MacPherson
We report an approach for cancer phenotyping based on targeted sequencing of cell-free DNA (cfDNA) for small cell lung cancer (SCLC). In SCLC, differential activation of transcription factors (TFs), such as ASCL1, NEUROD1, POU2F3, and REST defines molecular subtypes. We designed a targeted capture panel that identifies chromatin organization signatures at 1535 TF binding sites and 13,240 gene transcription start sites and detects exonic mutations in 842 genes. Sequencing of cfDNA from SCLC patient-derived xenograft models captured TF activity and gene expression and revealed individual highly informative loci...
April 12, 2024: Science Advances