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

© 2022 Global Journals The Genomics of Liposarcoma: A Review and Commentary important for proper development of multiple tissues and has high expression in the first three hours of adipogenesis of 3T3-L1 preadipocytes before decreasing in subsequent stages 88 . FGF signaling by adipocytic stem cells can induce HMGA2 expression 89 . Once turned on, it can bind Rb1 to displace HDAC1 from Rb/E2F at their binding sites, leading to activated E2F1 and cell cycle progression 90 . It is upregulated in lipomas and transgenic mice that overexpress HMGA2 result in hyperplasia of white adipose tissue 91,92 . These data suggest that HMGA2 alone cannot induce tumor progression and may only provide the proliferative context under which liposarcoma form. PTPRQ: PTPRQ is a protein phosphatidylinositol phosphatase (PIPase) whose over expression would prevent adipocyte differentiation from mesenchymal stem cells 93 . Gain in PTPRQ on chr12q21 was observed in 46% of DDLPS 8 . YEATS4: By inhibiting the promoters of p14 and p21, YEATS4 (GAS4) represses the p53 pathway 94 . Knockdown of YEATS4 in non-small cell lung cancer cells leads to increased expression of p21, p53 and PARP cleavage 95 . 1 Year 2022 2 Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Besides chr12q, other copy number alterations involved in adipocyte differentiation are aberrant in WDLPS and DDLPS. Loss of methylation within the promoter of CEBPA (chr19q13) may explain the lower expression of CEBPA in DDLPS than in WDLPS 66 . Gains in chr17p11 in DDLPS result in additional histologic features that are akin to UPS 96 . Gains in oncogenes that block adipocytic differentiation have been seen: JUN (chr1p32) 97 and YAP1 (chr11q22) 98,99 . Lipid metabolism may be aberrant in DDLPS as losses and subsequent lower expression of genes such as PLIN2 (chr9p22), LIPE (chr19q13), DLAT (chr11q23-24), and ACAD8 (chr11q23-24) occur more often in DDLPS as compared to other sarcoma types 8,96 . Rearrangement of SYT1 (calcium channel) was observed in WDLPS 100 . The level of heterogeneity and genomic complexity delineates differences between WDLPS and DDLPS. DDLPS have a higher number of point mutations that appear to be caused by the genome editing protein APOBEC (mutation signatures COSMIC2 and 13) 8 . However, these point mutations may not contribute to the etiology of disease (passenger events) as the number was positively associated with age, largely nonfunctional, and not known to be cancer drivers 8,35 . DDLPS also harbor higher number of rearrangements and copy number alterations than WLPS 35,101 . In fact, the frequency of somatic copy number alterations was highest in DDLPS when compared against LMS, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), and malignant Figure 5: The role of genes from chr12 (in red) that are frequently amplified in WDLPS and DDLPS in adipocytic differentiation and tumor growth. The differentiation state of the tumor cell may affect the impact of these genes. Therefore, the selection of these genes for amplification may be determined by the cell differentiation state. FRS and DDIT3 have documented activities affecting the CEBP transcription factors that direct earlier adipocytic progenitors while YEATS4 , HMGA2 , and PTPRQ appear to affect the later pre-adipocytic stages