The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.

中文翻译：

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肺癌肉瘤肿瘤异质性的分子和表达特征

肺癌肉瘤 (PCS)、癌和肉瘤这两个组成部分的遗传一致性和异质性由于其罕见发生而尚未完全阐明。我们对四种 PCS 的癌和肉瘤成分进行了靶向测序，以确定遗传相似性和差异。对福尔马林固定的石蜡包埋的组织样本进行宏观或微观解剖。从每个成分中提取 DNA，并分别分析遗传改变。此外，我们对一台 PCS 的两个组件进行了 RNA-seq 分析，以比较基因表达谱的差异。癌部分为腺癌2例，鳞癌1例，腺鳞癌1例。TP53在来自躯干的三个样本中观察到突变，尽管在一个病例中仅在肉瘤部分检测到突变。没有观察到特定的驱动基因突变；然而，在躯干中的一个病例中观察到了KRAS突变。RNA-seq 分析显示，横纹肌肉瘤成分表达了与肌肉发育相关的各种基因，而癌成分则没有；并且这两种成分之间的基因表达总体上是完全不同的。我们的研究表明，在大多数情况下，PCS 的两种不同成分具有共同的基因突变。尽管成分之间的基因表达不同，但如果在 PCS 中检测到KRAS等驱动基因，即使肿瘤含有肉瘤成分，分子靶向治疗也可能是有益的。