Global Journal of Science Frontier Research, G: Bio-Tech & Genetics, Volume 22 Issue 2

Figure 2: Survival and differentiation states of various liposarcoma subtypes Dedifferentiated liposarcoma has the worst outcome, followed by pleomorphic, round-cell, then well-differentiated, and finally myxoid liposarcoma 22 . Gene expression and DNA methylation patterns in lipoma and liposarcoma subtypes are similar to those seen during the various stages along the differentiation pathway of mesenchymal stem cells as they progress towards becoming mature adipocytes. In concordance with these observations in liposarcoma, a recent hallmark of cancer – phenotypic plasticity – was recently added describing mechanisms associated with disrupted differentiation. The mechanisms are divided into three classes – dedifferentiation of mature cells to a progenitor or stem-like state, blocked differentiation preventing progenitor cells from maturing, and trans differentiation enabling switching between lineages. It is likely that dedifferentiation and blocked differentiation occur in the various liposarcoma subtypes and that these two mechanisms are intertwined and held in place through mutations or epigenetic patterns. IV. L iposarcoma F ormation through G enetic L oss Patients with Li-Fraumeni syndrome and retinoblastoma have germline mutations of TP53 and RB1 , respectively, which leads to the formation of various tumor types, including high incidences of sarcomas as second and concurrent malignancies 23 . In Li-Fraumeni patients, these include liposarcoma, which occur less frequently than other sarcoma subtypes such as osteosarcoma, leiomyosarcoma (LMS), and rhabdomyosarcoma 24,25 . In like manner, retinoblastoma patients also occasionally develop liposarcoma, the majority of sarcoma risk being bone tumors, fibrosarcoma, rhabdomyosarcoma, and pleomorphic sarcomas 23 . Therefore, there is evidence that these canonic cancer genes are responsible for driving liposarcoma initiation. Sarcoma tumor initiation by mutation of TP53 and RB1 tumor suppressor genes have been demonstrated in vivo . Genetically engineered mouse or rat models of TP53 mutants develop sarcomas, namely angiosarcoma, osteosarcoma, and rhabdomyosarcoma with high levels of genomic instability 26-30 . Deletion of both TP53 and RB1 genes in mice leads to lower tumor generation time, resulting in greatly reduced survival than is seen when each gene is mutated alone 31 . When both TP53 and PTEN are simultaneously deleted specifically within adipose tissue, spontaneous generation of all four subtypes of liposarcoma occur 32 . This model underscores the importance of the TP53 and PI3K/AKT pathways in the initiation of liposarcoma, which may be partly due to the way in which they activate the Notch signaling pathway 33 . The effect of the 1 Year 2022 17 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) The Genomics of Liposarcoma: A Review and Commentary