肺腺癌转移器官倾向性的基因组绘图分析

2023-05-17 09:37

我们分析了2,532例肺腺癌（LUAD），以识别与转移、转移负荷、器官倾向性和无转移生存相关的临床病理和基因组特征。

SCI 16 May 2023

Genomic mapping of metastatic organotropism in lung adenocarcinoma

（IF: Cancer Cell, 38.585）

Lengel HB, Mastrogiacomo B, Connolly JG, Tan KS, Liu Y, Fick CN, Dunne EG, He D, Lankadasari MB, Satravada BA, Sun Y, Kundra R, Fong C, Smith S, Riely GJ, Rudin CM, Gomez DR, Solit DB, Berger MF, Li BT, Mayo MW, Matei I, Lyden DC, Adusumilli PS, Schultz N, Sanchez-Vega F, Jones DR. Genomic mapping of metastatic organotropism in lung adenocarcinoma. Cancer Cell. 2023 May 8;41(5):970-985.e3. doi: 10.1016/j.ccell.2023.03.018. Epub 2023 Apr 20. PMID: 37084736.

Correspondence:sanchezf@mskcc.org (F.S.-V.), jonesd2@mskcc.org (D.R.J.)

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.

我们分析了2,532例肺腺癌（LUAD），以识别与转移、转移负荷、器官倾向性和无转移生存相关的临床病理和基因组特征。发生转移的患者是年龄较轻的男性，原发性肿瘤富含微乳头状或实体组织学亚型，并具更高的突变负荷、染色体不稳定性和基因组倍增率。TP53、SMARCA4和CDKN2A的失活与特定部位转移时间的缩短相关。APOBEC突变特征在转移瘤中更为普遍，尤其是肝脏病变。对匹配标本的分析表明，原发性肿瘤和转移瘤之间通常共享相同的致癌和可操作的基因变异，但意义不明的基因拷贝数变异往往是转移瘤特有的。只有4%的转移灶具有在其匹配的原发灶中未检测到的可供用于治疗操作的变异。我们队列中的关键临床病理和基因组变异得到了外部验证。总的来说，我们的分析强调了临床病理学特征和肿瘤基因组学在LUAD器官倾向性中的复杂性。