Clinical and Molecular Spectrum of Liposarcoma.
Clinical and Molecular Spectrum of Liposarcoma.
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DOI：
10.1200/jco.2017.74.9598
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发表时间：
2018-01-10
期刊：
影响因子：
--
通讯作者：
Jones RL
中科院分区：
文献类型：
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作者：
Lee ATJ;Thway K;Huang PH;Jones RL
脂肪肉瘤是一种罕见的脂肪细胞分化的恶性肿瘤。将脂肪肉瘤分为四种主要亚型反映了这些疾病不同的临床表现、治疗敏感性和潜在的生物学特征。越来越多的临床管理决策和研究性治疗的发展是通过对亚型特异性分子病理学的更好理解来了解的。分化良好的脂肪肉瘤是最常见的亚型，与惰性行为、局部复发和对放疗和化疗不敏感有关。去分化脂肪肉瘤代表分化良好的疾病发展为更具侵袭性、转移性和致命性的恶性肿瘤。这两种亚型的特征在于12号染色体内的反复扩增，导致疾病驱动基因的过表达，这一直是治疗靶向的焦点。粘液样脂肪肉瘤的特征是特异性染色体易位，导致致癌融合蛋白，而多形性脂肪肉瘤是核型复杂，预后特别差的亚型，占不到10%的脂肪肉瘤诊断。一系列旨在靶向脂肪肉瘤特异性生物学的新型药物正在积极研究中，并为复发性或不可手术疾病的有限治疗选择提供了希望。
Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical behavior, treatment sensitivity, and underlying biology encompassed by these diseases. Increasingly, clinical management decisions and the development of investigational therapeutics are informed by an improved understanding of subtype-specific molecular pathology. Well-differentiated liposarcoma is the most common subtype and is associated with indolent behavior, local recurrence, and insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma represents focal progression of well-differentiated disease into a more aggressive, metastasizing, and fatal malignancy. Both of these subtypes are characterized by recurrent amplifications within chromosome 12, resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal translocation that results in an oncogenic fusion protein, whereas pleomorphic liposarcoma is a karyotypically complex and especially poor-prognosis subtype that accounts for less than 10% of liposarcoma diagnoses. A range of novel pharmaceutical agents that aim to target liposarcoma-specific biology are under active investigation and offer hope of adding to the limited available treatment options for recurrent or inoperable disease.