与其他部位的肿瘤和老年患者相比，儿童早期的中线低级别胶质瘤（mLGG）的预后较差。 LGGs 与 RAS-RAF-MEK 通路的异常激活有关，对该通路的药理学抑制具有治疗前景。本研究的目的是婴儿 mLGG 的临床和分子特征，重点是靶向激酶抑制的功效。本研究纳入了 40 名年龄 <3 岁的 mLGG 患者。根据国际儿科肿瘤学会 LGG 2004 年指南，大多数患者 (30/40) 接受了一线化疗 (CT)。通过聚合酶链反应和RNA测序对所有患者的肿瘤组织进行分子遗传学研究。中位随访时间为 3.5 年。30 名接受者中有 24 人的一线 CT 失败。确定的分子谱包括 26 名患者的 KIAA1549::BRAF 融合、6 名患者的 BRAF V600E、2 名患者的 FGFR1::TACC1 融合以及 4 名患者的罕见融合转录本。在疾病进展时，根据分子发现，对 27 名患者（其中 22 名患者接受了曲美替尼治疗）开始了靶向治疗 (TT)。 TT 治疗的中位时间为 16 个月，在评估疗效的 26 名患者中，有 12 名患者 (46%) 实现了部分缓解。仅在曲美替尼单药治疗中检测到严重不良事件：四名患者出现胃肠道或尿道粘膜急性损伤，并发出血和输血依赖性贫血，三名患者出现 3 级皮肤毒性。 儿童早期的 mLGG 往往是侵袭性肿瘤，对CT，并且经常需要替代治疗。大多数患者具有可药物化的分子靶点并对分子 TT 产生反应。

Midline low-grade gliomas (mLGGs) of early childhood have a poorer prognosis compared with tumors of other localizations and in older patients. LGGs are associated with aberrant activation of RAS-RAF-MEK pathway, and pharmacological inhibition of the pathway has therapeutic promise. The aim of this study was clinical and molecular characterization of infantile mLGGs, with emphasis on the efficacy of targeted kinase inhibition.This study enrolled 40 patients with mLGG age <3 years. The majority of the patients (30/40) received first-line chemotherapy (CT) as per International Society of Paediatric Oncology LGG 2004 guidelines. In all patients, molecular genetic investigation of tumor tissue by polymerase chain reaction and RNA sequencing was performed. The median follow-up was 3.5 years.First-line CT failed in 24 of 30 recipients. The identified molecular profiles included KIAA1549::BRAF fusions in 26 patients, BRAF V600E in six patients, FGFR1::TACC1 fusions in two patients, and rare fusion transcripts in four patients. At disease progression, targeted therapy (TT) was initiated in 27 patients (22 patients received trametinib) on the basis of molecular findings. TT was administered for a median of 16 months, with partial response achieved in 12 of 26 (46%) patients in which response was evaluated. Severe adverse events were detected only on trametinib monotherapy: acute damage of GI or urinary mucosa complicated by hemorrhage and development of transfusion-dependent anemia in four patients and grade 3 skin toxicity in three patients.mLGGs of early childhood are often aggressive tumors, resistant to CT, and frequently require alternative treatment. The majority of patients harbor druggable molecular targets and respond to molecular TT.