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

PRMT family, namely PRMT1, regulates their nucleo- cytoplasmic localization and binding to DNA 119 . Rearrangements involving FUS and EWSR1 with other C-terminal partnersoccur in various other cancer and sarcoma subtypes. For instance, FUS-ATF1 was found in an angiomatoid fibrous histiocytoma 120,121 , FUS- ERG occurs in acute myeloid leukemia 122,123 , FUS- BBF2H7 in low grade fibromyxoid sarcoma 124 , and FUS/EWSR1-KLF17 in myoepithelial tumors 125 In an analogous way, EWSR1- WT1 and EWSR1-FLI1 occur in Ewing Sarcoma and desmoplastic small round cell tumor (DSRCT), respectively 126,127 . Since the FET family forms the N-terminal partner, the C-terminal part of the fusion may affect protein interactions, differentiation state and the cell type that ultimately becomes malignant 116 . For myxoid liposarcoma, DDIT3 may affect fat differentiation, while other partners such as WT1 for Ewing Sarcoma and DSRCT (EWSR1-WT1 translocation) influence other tissue types . I n addition, point mutations of FUS are frequently observed in patients with amyotrophic lateral sclerosis (ALS) 128-130 . These mutations disrupt the nuclear localization sequence so that FUS remains in the cytoplasm 131 . Therefore, the type of mutation within a specific gene can drive different, unrelated diseases. Also, the mechanisms by which similar translocations diseases depends on the partners involved. Thus, comparisons of these mechanisms in various disease types may elucidate the roles of each translocation partner in disease generation as well as inform as to whether we can combine patients with these different diseases into basket trials for novel therapeutic options. Other distinguishing genomic features have been described for myxoid liposarcoma. The presence of the testis antigen NY-ESO-1 is thought to differentiate myxoid liposarcoma from other myxoid tumors 132 . TERT promoter mutations are the most frequent in myxoid liposarcoma as compared to other sarcomas 43 . Activating mutations in PIK3CA are the most common in myxoid liposarcoma as compared to other major liposarcoma histotypes 34 , with greater incidence in round cell myxoid liposarcoma 133 . These mutations appear to be mutually exclusive with PTEN loss and IGF1R expression 133 . In addition, patients with PIK3CA mutations in the helical or kinase domains have a shorter disease-specific survival than those with wild type PIK3CA 134 . Lower survival is also associated with methylation of the p14(ARF) promoter that leads to lower expression of ARF 135,136 . Higher proliferative activity in MLPS is associated with high levels of β‐ catenin 137 whereas growth through angiogenesis may be positively influenced by the hypermethylation and down regulation of the extracellular matrix glycoprotein EFEMP1, as compared to normal fat 19 . VIII. P leomorphic L iposarcoma (PLPS) IX. C urrent and F uture G enomics a) Single Cell Sequencing Despite the recent advances in understanding liposarcoma biology, there is still much to unravel in order to find effective targeted therapies for recurrent or metastatic lesions. Questions remain on how we can effectively explore themes within the complex heterogeneity of liposarcoma including degrees of adipocytic differentiation, mixed phenotype or clonal subtype, and cell of origin, which may enable avenues to potential therapeutics. Recently, single-cell sequencing (SCS) has made a dramatic impact on the field of cancer by revealing novel cell/differentiation states, exploring inter- and intra-tumor heterogeneity, and discovering rare cell populations previously undetected. Since Macosko et al. and Klein et al. developed Drop-Seq and in Drop respectively in 2015, approximately 14,534 articles were found using the keywords ‘single-cell’ and ‘sequencing’ to search in PubMed 146,147 . Among those articles, 68 contained the word ‘sarcoma’, and 5 contained ‘liposarcoma’. This suggests that SCS is not being effectively used to explore sarcoma and liposarcoma genomics given the prevalence of SCS within the last decade. In the following section, we will discuss applying various SCS technologies to liposarcoma genomics, describe the common pitfalls when approaching liposarcomas, and 1 Year 2022 23 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) The Genomics of Liposarcoma: A Review and Commentary and possibly others 116 . Arginine methylation by the The definition of this particular subtype is the presence of pleomorphic lipoblasts 138 . It is found frequently in the extremities of older adults, with those within upper extremities having poorer survival 139 . This subtype excludes the distinguishing mutations found in the other subtypes described above: no fusions involving DDIT3 and no consistent amplification of MDM2 140 . It has a more complex karyotype than other liposarcoma subtypes 141,142 , which may explain why these patients have the shortest survival of all liposarcoma subtypes. This complex karyotype nature of PLPS may form the basis for its pathologic and copy number profile resemblance to undifferentiated pleomorphic sarcoma (UPS) 138,143 . Both had gains in: 1p, 1q, 5p, 19q, and 20q and recurrent losses in 1q, 2q, 3p, 4q, 10q, 11q, and 13q (including RB1 ). When comparing PLPS karyotypes among multiple complex karyotype pleomorphic sarcomas 144 , the frequency of chromosomal aberrations was the fewest in pleomorphic liposarcoma. Thus, these may not be as advanced in complexity and severity as other pleomorphic sarcoma. Missense TP53 mutations within exons 5-9 were found in 60% of the 31 cases that were examined 141,142 , low levels of Rb1, and other features such as phyllodes of the breast 145 which occur more frequently in women with Li Fraumeni Syndrome ( TP53 germline mutation).