Chordoma is a rare bone tumor that is typically resistant to chemotherapy and is associated with genetic abnormalities of the T-box transcription factor T (TBXT) gene, which encodes the transcription factor brachyury. Brachyury is felt to be a major contributor to the development of chordomas. We describe a 67-year-old woman who developed an undifferentiated pleomorphic sarcoma in her thigh. Despite treatment with standard chemotherapy regimens, she had a rapidly progressive course of disease with pulmonary metastases and passed away 8 months from diagnosis with pulmonary complications. Her medical history was remarkable in that she had a spheno-occipital chordoma at age 39 and later developed multiple other tumors throughout her life including Hodgkin lymphoma and squamous cell carcinoma and basal cell carcinoma of the skin. She had a family history of chordoma and her family underwent extensive genetic study in the past and were found to have a duplication of the TBXT gene. Brachyury has been found to associate with tumor progression, treatment resistance, and metastasis in various epithelial cancers, and it might play roles in tumorigenesis and aggressiveness in this patient with multiple rare tumors and germ line duplication of the TBXT gene. Targeting this molecule may be useful for some malignancies.

中文翻译：

---

家族性脊索瘤患者多发恶性肿瘤一例

脊索瘤是一种罕见的骨肿瘤，通常对化疗耐药，并且与编码转录因子 brachyury 的 T-box 转录因子 T (TBXT) 基因的遗传异常有关。Brachyury 被认为是脊索瘤发展的主要贡献者。我们描述了一名 67 岁的女性，她的大腿出现未分化的多形性肉瘤。尽管采用标准化疗方案进行治疗，但她的病程进展迅速，伴有肺转移，并在诊断出肺部并发症后 8 个月去世。她的病史引人注目，因为她在 39 岁时患有蝶枕脊索瘤，后来在她的一生中发展了多种其他肿瘤，包括霍奇金淋巴瘤、鳞状细胞癌和皮肤基底细胞癌。她有脊索瘤家族史，她的家人过去接受了广泛的基因研究，发现有一个重复的 TBXT 基因。已发现 Brachyury 与各种上皮癌的肿瘤进展、治疗抗性和转移有关，并且它可能在这名患有多种罕见肿瘤和 TBXT 基因种系重复的患者的肿瘤发生和侵袭性中发挥作用。靶向这种分子可能对某些恶性肿瘤有用。它可能在这名患有多发罕见肿瘤和 TBXT 基因种系重复的患者的肿瘤发生和侵袭性中发挥作用。靶向这种分子可能对某些恶性肿瘤有用。它可能在这名患有多发罕见肿瘤和 TBXT 基因种系重复的患者的肿瘤发生和侵袭性中发挥作用。靶向这种分子可能对某些恶性肿瘤有用。