BACKGROUND Multifocal lung cancers (MLCs) are common in patients newly diagnosed with lung cancer, and histological results of most synchronous MLCs are similar. Few cases with different histology findings have been reported, and no genomic or transcriptomic profiling of this kind of cases were done before. Here, we analyzed genomic and transcriptomic profiles of all lung tumors from 2 patients with synchronous adenocarcinoma and squamous cell carcinoma in the same lung lobe. CASE PRESENTATION Two patients were diagnosed as synchronous adenocarcinoma and squamous cell carcinoma and underwent surgical resection. All 4 tumors showed distinct genomic profiles, therefore were independent primary tumors. Several cancer-associated pathways, such as RTK-RAS pathway and Notch pathway, exhibited different mutated genes in different tumors from the same patient. Several known cancer genes with different mutations, including TP53 and KEAP1, were also detected. Mutation signature analysis demonstrated that the tumor initiation might be related to the transcription coupled nucleotide excision repair process. Two tumors for these 2 patients had loss of heterogeneity (LOH) in HLA genes, showing tumor escaping mechanism. Furthermore, tumor microenvironments showed different patterns in 2 tumors from the same patient. The tumor with more neoantigens and no HLA LOH showed more infiltrating CD8+ T cells and more clonal TCRs, indicating a more active microenvironment. CONCLUSIONS The lung squamous cell carcinoma and lung adenocarcinoma form the same patient are from independent origins. The genetic profiles and transcriptomic microenvironments are quite different for these 2 tumors. With the same genetic background, the 2 tumors in one patient exhibited different tumor escape mechanisms and immune responses, including HLA LOH and T cell infiltrating and expansion.

中文翻译：

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2例同步肺腺癌和肺鳞状细胞癌患者的基因组概况和转录组微环境：一例报告。

背景技术多灶性肺癌（MLC）在新诊断为肺癌的患者中很常见，大多数同步MLC的组织学结果相似。很少有具有不同组织学发现的病例报告，并且以前没有进行过此类病例的基因组或转录组分析。在这里，我们分析了同一肺叶中2例同步腺癌和鳞状细胞癌患者的所有肺部肿瘤的基因组和转录组谱。病例介绍2例患者被诊断为同步性腺癌和鳞状细胞癌，并接受了手术切除。所有4种肿瘤均显示出独特的基因组谱，因此是独立的原发性肿瘤。几种与癌症相关的途径，例如RTK-RAS途径和Notch途径，在同一患者的不同肿瘤中显示出不同的突变基因。还检测到了几种已知的具有不同突变的癌症基因，包括TP53和KEAP1。突变特征分析表明，肿瘤的发生可能与转录偶联核苷酸切除修复过程有关。这2例患者中有2例肿瘤的HLA基因丧失了异质性（LOH），显示出肿瘤逃逸机制。此外，同一位患者的2个肿瘤的肿瘤微环境表现出不同的模式。具有更多新抗原且没有HLA LOH的肿瘤显示出更多的浸润性CD8 + T细胞和更多的克隆TCR，表明微环境更为活跃。结论同一患者的肺鳞癌和肺腺癌来自不同的国家。这两种肿瘤的遗传特征和转录组微环境差异很大。具有相同的遗传背景，一名患者的2种肿瘤表现出不同的肿瘤逃逸机制和免疫反应，包括HLA LOH和T细胞的浸润和扩展。