Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma
Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma
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DOI：
10.1016/j.ccr.2010.12.023
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发表时间：
2011-02-15
期刊：
影响因子：
50.3
通讯作者：
Keller, Charles
中科院分区：
文献类型：
--
作者：
Rubin, Brian P.;Nishijo, Koichi;Keller, Charles
胚胎性横纹肌肉瘤（eRMS）在肉瘤中表现出最多的肌分化，但确切的细胞起源仍不清楚。利用Ptch1， p53和/或Rb1条件小鼠模型和控制产前或产后肌源性细胞，我们证明了eRMS和未分化多形性肉瘤（UPS）处于连续统一体，卫星细胞倾向于产生UPS。相反，成熟的成肌细胞中p53的缺失会产生具有最高肌分化潜力的eRMS。无论来源如何，Rb1的丢失改变了肿瘤表型，以模仿UPS。在缺乏致病性染色体易位的人肉瘤中，p53的功能丧失是普遍存在的，而Shh或Rb1的改变可能主要起修饰作用。因此，肉瘤的表型受到细胞起源和突变谱的强烈影响。
Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.