Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Biomarker Development Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Commun. 2023 Aug 17;14(1):4980. doi: 10.1038/s41467-023-40793-x.
Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.
多达 50%的非小细胞肺癌 (NSCLC) 患者会发生脑转移 (BM)，但 BM 基因组学的研究受到组织获取、不完整的临床数据以及缺乏与配对颅外标本比较的限制。在这里，我们报告了一个由 233 名接受过切除和测序 (MSK-IMPACT) 的 NSCLC BM 患者组成的队列，以及全面的临床数据。通过匹配样本（47 个原发性肿瘤，42 个颅外转移），我们发现 BM 样本中 CDKN2A/B 缺失和细胞周期通路改变富集。注意到有意义的临床基因组相关性，即 LMD 中的 EGFR 改变和多灶性区域性脑进展中的 MYC 扩增。发生早期 LMD 的患者经常具有罕见、多个和持续可检测的 EGFR 驱动突变。与其他组织部位相比，BM 标本中鉴定出的不同突变模式表明颅内进展有特定的生物学基础。
