我们分析了2,532例肺腺癌（LUAD），以识别与转移、转移负荷、器官特异性和无转移生存相关的临床病理和基因组特征。发生转移的患者通常年轻且为男性，原发肿瘤富含微小乳头状或实性组织学亚型，并具有更高的突变负荷、染色体不稳定性和基因组倍增率。TP53、SMARCA4和CDKN2A基因失活与特定部位更短的转移时间相关。APOBEC突变标记在转移病灶中更为常见，尤其是肝脏病变。匹配标本的分析表明，原发肿瘤和转移病灶之间经常共享致癌和可操作的变异，而未知意义的拷贝数变异则更多地出现在转移病灶中。只有4％的转移病灶携带在配对原发病灶中未检测到的可治疗变异。我们队列中的关键临床病理和基因组变异已得到外部验证。总之，我们的分析突显了LUAD器官特异性的临床病理和肿瘤基因组的复杂性。 版权所有 © 2023 Elsevier Inc。

We analyzed 2,532 lung adenocarcinomas (LUAD) to identify the clinicopathological and genomic features associated with metastasis, metastatic burden, organotropism, and metastasis-free survival. Patients who develop metastasis are younger and male, with primary tumors enriched in micropapillary or solid histological subtypes and with a higher mutational burden, chromosomal instability, and fraction of genome doublings. Inactivation of TP53, SMARCA4, and CDKN2A are correlated with a site-specific shorter time to metastasis. The APOBEC mutational signature is more prevalent among metastases, particularly liver lesions. Analyses of matched specimens show that oncogenic and actionable alterations are frequently shared between primary tumors and metastases, whereas copy number alterations of unknown significance are more often private to metastases. Only 4% of metastases harbor therapeutically actionable alterations undetected in their matched primaries. Key clinicopathological and genomic alterations in our cohort were externally validated. In summary, our analysis highlights the complexity of clinicopathological features and tumor genomics in LUAD organotropism.Copyright © 2023 Elsevier Inc. All rights reserved.