A review of retroperitoneal liposarcoma genomics

Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes -well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) -they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting. This review explores the current understanding of the genomic landscape in retroperitoneal liposarcoma and the consequences on therapeutic strategy. The anatomical focus on the retroperitoneum, rather than the extremity is undertaken for several reasons. Firstly, a summary of specific retroperitoneal liposarcoma genomics is lacking in the literature. This would be useful to clinicians and scientists alike, dealing with this specific disease in the era of personalised medicine. Secondly, it is well established that variations in the tumour microenvironment can determine response to therapy. Lastly, RPL carries a poorer prognosis than extremity LS, has a distinct natural history and is managed differently.