寡转移性非小细胞肺癌和相应脑转移的基因谱。
Genetic profiles of oligometastatic non-small cell lung cancer and corresponding brain metastases.
发表日期:2024 May 25
作者:
Raphael S Werner, Markus Rechsteiner, Holger Moch, Alessandra Curioni-Fontecedro, Michael Weller, Tobias Weiss, Luca Regli, Emilie Le Rhun, Fabian Mairinger, Isabelle Opitz, Alex Soltermann
来源:
Brain Structure & Function
摘要:
在寡转移性非小细胞肺癌患者中,全身治疗与原发肿瘤和所有转移部位的局部消融治疗相结合可改善预后。对于患者选择和治疗分配,需要进一步了解寡转移状态的分子特征。在这里,我们对原发性非小细胞肺癌和相应的脑转移进行了基因表征。我们回顾性地鉴定了接受过少转移性非小细胞肺癌和同步(<3个月)或异时(>3个月)脑转移的患者手术切除原发肿瘤和脑转移瘤。使用 Oncomine 焦点分析组通过靶向下一代测序对福尔马林固定石蜡包埋的肿瘤细胞块进行突变分析。46 个配对样本的测序成功。 31 个原发肿瘤 (67.4%) 和 40 个脑转移瘤 (86.9%) 中存在致癌改变。 31例中,29例(93.5%)在相应的脑转移瘤中保留了原发肿瘤的改变。原发性肿瘤和脑转移瘤中最常见的致癌驱动因素是 KRAS 突变 (n = 21)。在 16 名患者 (34.8%) 中,脑转移灶存在额外的致癌改变。脑转移中存在私人基因改变是较短总生存期的独立预测因素。在寡转移性非小细胞肺癌中,脑转移保留了原发肿瘤的主要基因改变。患者可能会受益于突变 KRAS 的靶向抑制。脑转移中额外的私人基因改变令人沮丧。© 作者 2024。由牛津大学出版社代表欧洲心胸外科协会出版。
In patients with oligometastatic non-small cell lung cancer, systemic therapy in combination with local ablative treatment of the primary tumor and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary non-small cell lung cancer and corresponding brain metastases.We retrospectively identified patients with oligometastatic non-small cell lung cancer and synchronous (<3 months) or metachronous (>3 months) brain metastases who underwent surgical resection of both primary tumor and brain metastases. Mutation profiling of formalin-fixed paraffin-embedded tumor cell blocks was performed by targeted next generation sequencing using the oncomine focus assay panel.Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumors (67.4%) and 40 brain metastases (86.9%). The alteration of the primary tumors was preserved in the corresponding brain metastases in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumors and brain metastases was a KRAS mutation (n = 21). In 16 patients (34.8%), the brain metastasis harbored additional oncogenic alterations. The presence of a private genetic alteration in the brain metastasis was an independent predictor of shorter overall survival.In oligometastatic non-small cell lung cancer, brain metastases retain the main genetic alterations of the primary tumors. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the brain metastases are dismal.© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.