DR-323 clusterCUP

Tumors are classified mainly by their cell of origin. Large cell neuroendocrine carcinomas are rare lung tumors and clinical studies for the treatment of these tumors have difficulties finding enough patients to enroll. Unlike for other lung tumors, the cell of origin of LCNECs is unclear. (Immuno)histologically, the tumors show both features of non-small cell lung cancers (NSCLC) and neuroendocrine tumors. We will use ‘regional mutational densities’ (RMDs), as a marker of open and closed chromatin to find the cell of origin of these tumors. We will apply unsupervised clustering of the RMD-features, to discover how these tumors cluster in comparison with lung adenocarcinomas (NSCLC), lung squamous cell carcinomas (NSCLC) and lung small cell carcinomas (neuroendocrine carcinoma). We hope to find biologically informed evidence for the cell of origin of LCNECs in order to improve the classification of lung tumors. As controls we will use different tumor types, to make sure that the clusters discovered are able to differentiate tumors from different organs or different cell types (carcinomas, sarcomas). We will also use available RNA-seq data to show that the basis for RMD’s is open and closed chromatin and the associated respective expression of genes and suppression of genes.

Kim Monkhorst, Nederlands Kanker Instituut – Antoni van Leeuwenhoek, the Netherlands