Cornelius Courts

Micro-RNAs (miRNAs) are a class of small noncoding RNA (ncRNA) molecules with a length of 18-24 nucleotides which play an essential regulative role for many cellular processes. Evidence suggests that the miRNome is a more precise and meaningful representation of a cell type and condition than the mRNA transcriptome. To identify miRNAs that are suitable for forensic body-fluid identification, a global screening by microarray analysis of c. 800 miRNAs of forensic blood and saliva samples was performed, and by bioinformatic processing, three differentially expressed candidate miRNAs for saliva and blood each were selected. The six candidates were then validated and confirmed via quantitative PCR. Herein, we present miRNA assays consisting of three differentially expressed miRNAs for the identification of blood (miR-126, miR-150, miR-451) and saliva (miR-200c, miR-203, miR-205), respectively. We conclude that miRNA extraction from forensic samples is possible and support a "proof of concept" that body-fluid identification by miRNA analysis may become a potent forensic technique.

. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.