Mariño-Enríquez Adrián, Bovée Judith V M G
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Surg Pathol Clin. 2016 Sep;9(3):457-73. doi: 10.1016/j.path.2016.04.009.
Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype.
肉瘤是罕见的间充质肿瘤，具有显著的形态学和分子异质性。肉瘤的分子研究为形态学分类提供了细化，并（经常）提供诊断信息、（很少）进行预后分层以及（偶尔）预测治疗反应。在此，我们总结了肉瘤发病机制的主要分子机制，并介绍了临床上有用的肉瘤诊断、预后和预测分子标志物。讨论了五种主要的分子改变，并以代表性的肉瘤类型进行说明，包括：1. 血管肿瘤中嵌合转录因子的存在；2. 胃肠道间质瘤中异常的激酶信号传导；3. 软骨肉瘤、软骨母细胞瘤和其他肿瘤中的表观遗传失调；4. 去分化脂肪肉瘤中由于局灶性拷贝数改变导致的细胞存活和增殖失调；5. 传统骨肉瘤中极端的基因组不稳定性，作为具有高度复杂核型的肉瘤的代表例子。
