多原发性肺癌（MPLC）的发病率正在增加，我们的一些手术患者表现出大量病变。我们将具有五个或更多原发灶的肺癌定义为超级 MPLC。阐明这种特殊 MPLC 亚型的基因组特征有助于减轻疾病负担并了解肿瘤进化。在我们的同步超早期 MPLC 队列 (PUMCH-ssesMPLC) 中，对来自 18 名患者的 130 个切除的恶性标本进行全外显子组测序，提供了全面的超 MPLC 基因组图谱。 PI3k-Akt 和 MAPK 通路中突变丰富。其BRAF突变频率（31.5%）显着高于病灶较少和早期单病灶癌症的MPLC，而EGFR突变显着较少（13.8%）。随着病变数量的增加，BRAF 突变逐渐占主导地位。此外，侵袭性病变更倾向于具有经典的超级 MPLC 突变模式。高频 BRAF 突变（尤其是 II 类）和低频 EGFR 突变可能是超级 MPLC 患者靶向治疗效果有限的原因。© 2024。作者。

The incidence of multiple primary lung cancer (MPLC) is increasing, with some of our surgical patients exhibiting numerous lesions. We defined lung cancer with five or more primary lesions as super MPLCs. Elucidating the genomic characteristics of this special MPLC subtype can help reduce disease burden and understand tumor evolution. In our cohort of synchronous super early-stage MPLCs (PUMCH-ssesMPLC), whole-exome sequencing on 130 resected malignant specimens from 18 patients provided comprehensive super-MPLC genomic landscapes. Mutations are enriched in PI3k-Akt and MAPK pathways. Their BRAF mutation frequency (31.5%) is significantly higher than MPLC with fewer lesions and early-stage single-lesion cancer, while EGFR mutations are significantly fewer (13.8%). As lesion counts increase, BRAF mutations gradually become dominant. Also, invasive lesions more tend to have classic super-MPLC mutation patterns. High-frequency BRAF mutations, especially Class II, and low-frequency EGFR mutations could be a reason for the limited effectiveness of targeted therapy in super-MPLC patients.© 2024. The Author(s).