Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, Maryland 20892, USA.
Nat Rev Endocrinol. 2017 Aug;13(8):480-491. doi: 10.1038/nrendo.2017.16. Epub 2017 Mar 24.
Clinical outcomes and treatment modalities for osteosarcoma, the most common primary cancer of bone, have changed very little over the past 30 years. The peak incidence of osteosarcoma occurs during the adolescent growth spurt, which suggests that bone growth and pubertal hormones are important in the aetiology of the disease. Tall stature, high birth weight and certain inherited cancer predisposition syndromes are well-described risk factors for osteosarcoma. Common genetic variants are also associated with osteosarcoma. The somatic genome of osteosarcoma is highly aneuploid, exhibits extensive intratumoural heterogeneity and has a higher mutation rate than most other paediatric cancers. Complex pathways related to bone growth and development and tumorigenesis are also important in osteosarcoma biology. In this Review, we discuss the contributions of germline and somatic genetics, tumour biology and animal models in improving our understanding of osteosarcoma aetiology, and their potential to identify novel therapeutic targets and thus improve the lives of patients with osteosarcoma.
骨肉瘤是最常见的原发性骨癌，其临床结果和治疗方式在过去 30 年中几乎没有改变。骨肉瘤的发病高峰出现在青少年生长突增期，这表明骨骼生长和青春期激素在疾病的发病机制中起着重要作用。身材高大、出生体重高和某些遗传性癌症易感性综合征是骨肉瘤的明确危险因素。常见的遗传变异也与骨肉瘤有关。骨肉瘤的体细胞基因组高度非整倍体，表现出广泛的肿瘤内异质性，并且其突变率高于大多数其他儿科癌症。与骨骼生长和发育以及肿瘤发生相关的复杂途径在骨肉瘤生物学中也很重要。在这篇综述中，我们讨论了种系遗传学和体细胞遗传学、肿瘤生物学和动物模型在增进我们对骨肉瘤发病机制的理解方面的贡献，以及它们在确定新的治疗靶点方面的潜力，从而改善骨肉瘤患者的生活。
