Structural and functional genomics characterization of complex karyotype sarcomas for targeting perturbed telomere maintenance mechanisms

Sarcomas, just as other cancers, achieve replicative immortality by reactivating mechanisms that maintain the ends of their chromosomes, called telomeres. Complex genetics sarcomas, such as leiomyosarcoma, osteosarcoma, undifferentiated pleomorphic sarcomas, are a group of sarcomas with wide-spread genomic instability that have poor prognosis use a yet understudied mechanism to maintain telomere length, called alternative lengthening of telomeres (ALT). In this project, with help of genomics analysis of tumors and cell models, and CRISPR/Cas9-based kinome-focused functional genomic screens, we aim to 1) identify the molecular drivers and of ALT and 2) “druggable” dependencies of complex genetics sarcomas. This will improve understanding of the biology of complex karyotype sarcomas and reveal potential biology-guided treatment options for sarcomas that employ ALT.