Targeted Sequencing Analysis of Predominant Histological Subtypes in Resected Stage I Invasive Lung Adenocarcinoma.
Targeted Sequencing Analysis of Predominant Histological Subtypes in Resected Stage I Invasive Lung Adenocarcinoma.
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DOI：
10.7150/jca.51405
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发表时间：
2021
影响因子：
3.9
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Li Y;Tan Y;Hu S;Xie J;Yan Z;Zhang X;Zong Y;Han-Zhang H;Li Q;Li C
目的：肺腺癌（lung adenocarcinoma，LADC）可分为5种主要的组织学亚型：乳头状腺癌（papillary-predominant adenocarcinoma，PPA）、小乳头状腺癌（micropapillary-predominant adenocarcinoma，阿帕）、腺泡状腺癌（acinar-predominant adenocarcinoma，APA）和实性腺癌（solid-predominant adenocarcinoma，SPA）。然而，主要组织学亚型的突变谱尚未得到很好的定义。在这项研究中，我们的目的是揭示5个主要组织学亚型的基因组景观。患者和方法：我们对86例I期浸润性腺癌（IAC）患者进行了下一代测序（NGS），使用了包括168个癌症相关基因的定制面板。结果：我们的分析共发现了302个基因组变异。5种亚型显示不同的突变谱，LPA、阿帕、PPA、MPA和SPA的平均突变率分别为1.95（范围：0-5）、2.56（范围：1-6）、3.5（范围：1-7）、3.75（范围：1-8）和6.05（范围：2-12）（p=4.17e-06）。96.55%（83/86）的患者发生驱动基因突变。EGFR（73.3%）、KRAS（9.3%）、ALK（4.7%）和MET（4.7%）是最常见的突变肺癌驱动基因，TP 53是最常见的突变肿瘤抑制基因。SPA患者比LPA患者具有更多的驱动突变和更高的TP 53频率。有趣的是，据报道与高肿瘤突变负荷和对免疫治疗的更好反应相关的LRP 1B突变仅在5例SPA患者中检测到（p=0.001）。其他四个队列中没有患者携带LRP 1B突变。结论：我们揭示了LADC的5种主要组织学亚型的独特突变景观，其明显的平均突变率与SPA和LPA分别具有最高和最低的平均突变率。SPA患者的LRP 1B突变率和PD-L1阳性率较高，表明SPA患者可能对免疫治疗有更好的反应。
Objective: Lung adenocarcinoma (LADC) is classified into five main histological subtypes with distinct clinicopathologic characteristics: lepidic-predominant adenocarcinoma (LPA), acinar-predominant adenocarcinoma (APA), papillary-predominant adenocarcinoma (PPA), micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). However, the mutational profiles of predominant histological subtypes have not been well defined. In this study, we aimed to reveal the genomic landscape of 5 main histological subtypes. Patients and Methods: We performed next-generation sequencing (NGS) in a cohort of 86 stage I invasive adenocarcinoma (IAC) patients, using a customized panel including 168 cancer-associated genes. Results: Our analysis identified a total of 302 genomic alterations. Five subtypes showed different mutation profiles with LPA, APA, PPA, MPA and SPA had an average mutation rate of 1.95 (range: 0-5), 2.56 (range: 1-6), 3.5 (range: 1-7), 3.75 (range: 1-8) and 6.05 (range: 2-12), respectively (p=4.17e-06). Driver mutations occurred in 96.55% (83/86) of all patients. EGFR (73.3%), KRAS (9.3%), ALK (4.7%) and MET (4.7%) are the most commonly mutated lung cancer driver genes, TP53 is the top mutated tumor suppressor gene. SPA patients harbored more driver mutations and higher frequency of TP53 than LPA patients. Interestingly, LRP1B mutations, which has been reported to be associated with high tumor mutation burden and better response to immunotherapy, were only detected from 5 SPA patients (p=0.001). No patients from other four cohorts harbored LRP1B mutations. Conclusions: We revealed distinctive mutation landscape of the 5 major histological subtypes of LADC, evident by distinctive average mutation rate with SPA and LPA having the highest and lowest average mutation rate, respectively. SPA patients showed higher mutation rate of LRP1B and higher rates for PD-L1 positivity, indicating that SPA patients may have better response to immunotherapy.
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影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
6.4
作者：
Kwong, Francois Ng Kee;Laggner, Ute;Nicholson, Andrew G.
通讯作者：
Nicholson, Andrew G.
DOI：
10.1097/pas.0000000000000134
发表时间：
2014-04
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kadota K;Villena-Vargas J;Yoshizawa A;Motoi N;Sima CS;Riely GJ;Rusch VW;Adusumilli PS;Travis WD
通讯作者：
Travis WD
DOI：
10.1093/bioinformatics/btp698
发表时间：
2010-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Durbin R
通讯作者：
Durbin R
影响因子：
2.9
作者：
Dong, Yu-Jie;Cai, Yi-Ran;Zhang, Li
通讯作者：
Zhang, Li