Systematic identification of genomic markers of drug sensitivity in cancer cells

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.     

Histone acetylation in scrapie-affected mouse brain

Zusammenfassung Im Gehirn von Mäusen mit Traberkrankheit (Scrapie) war die Azetylierung von Histonen um 25% erhöht. Diese chemische Änderung erschien weitaus früher als klinische Symptome und histologisch-pathologische Veränderungen. Die Beziehung von Azetyl-Histonen zu Deoxyribonukleinsäuren und ihre Verhältnisse zur Aktivierung von spezifischen Nervenzellen werden kurz besprochen.