Sarcomas are heterogenous rare cancers that disproportionately affect the young, with a strong genetic etiology. We have created the largest sarcoma cohort to systematically map the genetic origins of sarcomas at the population level. We used whole genome sequencing and a case:control design to analyse more than 1,600 predominantly Caucasian-European patients with sarcomas, and more than ethnically-matched 3,500 elderly, well controls. We have developed a novel approach to studying whole-genome rare variant associations, in order to map known or likely pathogenic variation in currently actionable genes in the sarcoma population, and to identify novel pathways that drive tumor susceptibility. Our early results indicate a significant burden of pathogenic variation in known genes such as TP53, NF1, SDHB and SDHD; as well as more surprising genes such as BRCA2, those involved in mismatch repair. In addition, we have identified signals that suggest systematic involvement of pathways involved in telomere maintenance and the G2/M phase of the cell cycle. These results will be presented in detail at the meeting.