Li Haochen, Huang Zhicheng, Guo Chao, Wang Yadong, Li Bowen, Wang Sha, Bai Na, Chen Hanlin, Xue Jianchao, Wang Daoyun, Zheng Zhibo, Bing Zhongxing, Song Yang, Xu Yuan, Huang Guanghua, Yu Xiaoqing, Li Ruirui, Fung Ka Luk, Li Ji, Song Lan, Zhu Ziwei, Liu Songtao, Liang Naixin, Li Shanqing
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
School of Medicine, Tsinghua University, Beijing, 100084, China.
NPJ Precis Oncol. 2024 Oct 9;8(1):229. doi: 10.1038/s41698-024-00726-3.
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.
多原发性肺癌（MPLC）的发病率正在上升，我们的一些手术患者表现出大量病灶。我们将具有五个或更多原发性病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演变。在我们的同步超早期MPLC队列（PUMCH-ssesMPLC）中，对18例患者的130份切除的恶性标本进行全外显子组测序，提供了全面的超级MPLC基因组图谱。突变在PI3k-Akt和MAPK途径中富集。它们的BRAF突变频率（31.5%）显著高于病灶较少的MPLC和早期单病灶癌，而EGFR突变显著较少（13.8%）。随着病灶数量的增加，BRAF突变逐渐占主导地位。此外，侵袭性病灶更倾向于具有典型的超级MPLC突变模式。高频BRAF突变，尤其是II类，以及低频EGFR突变可能是超级MPLC患者靶向治疗效果有限的一个原因。
