美国纪念斯隆凯瑟琳研究所David R. Jones和Francisco Sanchez-Vega研究团队合作绘制出肺腺癌(LUAD)转移性器官倾向的基因组图谱。这一研究成果发表在2023年4月20日出版的国际学术期刊《癌细胞》上。
他们分析了2532例肺腺癌，以确定与转移、转移负荷、器官亲和性和无转移生存相关的临床病理和基因组特征。发生转移的患者多为年轻男性，原发肿瘤多为微乳头状或实体组织学亚型，具有较高的突变负荷、染色体不稳定性和基因组加倍率。TP53、SMARCA4和CDKN2A的失活与部位特异性转移时间缩短相关。APOBEC突变特征在转移瘤中更为普遍，尤其是肝脏病变。
对匹配样本的分析表明，原发肿瘤和转移瘤之间经常存在致癌和可治疗的改变，而未知意义的拷贝数改变往往是转移瘤所特有的。只有4%的转移灶在其匹配的原发灶中未发现具有治疗作用的改变。在这一队列中，关键的临床病理和基因组改变进行了外部验证。
总之，他们的分析强调了LUAD嗜器官性的临床病理特征和肿瘤基因组学的复杂性。
附：英文原文
Title: Genomic mapping of metastatic organotropism in lung adenocarcinoma
Author: Harry B. Lengel, Brooke Mastrogiacomo, James G. Connolly, Kay See Tan, Yuan Liu, Cameron N. Fick, Elizabeth G. Dunne, Di He, Manendra B. Lankadasari, Baby Anusha Satravada, Yichao Sun, Ritika Kundra, Chris Fong, Shaleigh Smith, Gregory J. Riely, Charles M. Rudin, Daniel R. Gomez, David B. Solit, Michael F. Berger, Bob T. Li, Marty W. Mayo, Irina Matei, David C. Lyden, Prasad S. Adusumilli, Nikolaus Schultz, Francisco Sanchez-Vega, David R. Jones
Issue&Volume: 2023-04-20
Abstract: We analyzed 2,532 lung adenocarcinomas (LUAD) to identify the clinicopathologicaland 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 andwith 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 mutationalsignature is more prevalent among metastases, particularly liver lesions. Analysesof matched specimens show that oncogenic and actionable alterations are frequentlyshared between primary tumors and metastases, whereas copy number alterations of unknownsignificance are more often private to metastases. Only 4% of metastases harbor therapeuticallyactionable alterations undetected in their matched primaries. Key clinicopathologicaland genomic alterations in our cohort were externally validated. In summary, our analysishighlights the complexity of clinicopathological features and tumor genomics in LUADorganotropism.
DOI: 10.1016/j.ccell.2023.03.018
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00091-0
Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx
本期文章：《癌细胞》：Online/在线发表
