Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Mol Carcinog. 2022 Oct;61(10):924-932. doi: 10.1002/mc.23448. Epub 2022 Jul 18.
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.
由于肺肉瘤样癌（PCS）的罕见发生，其癌性成分和肉瘤性成分的遗传一致性和异质性尚未完全阐明。我们对 4 例 PCS 的癌性和肉瘤性成分进行了靶向测序，以鉴定遗传上的相似性和差异性。对福尔马林固定石蜡包埋的组织样本进行了宏观或微观解剖。从每个成分中提取 DNA，并分别分析遗传改变。此外，我们对 1 例 PCS 的两个成分进行了 RNA-seq 分析，以比较基因表达谱的差异。在两个病例中，癌性部分为腺癌，1 个为鳞癌，1 个为腺鳞癌。TP53 突变在 3 个来源于躯干的样本中观察到，但在 1 个病例中仅在肉瘤部分检测到。未观察到特定的驱动基因突变；然而，在 1 个躯干病例中观察到 KRAS 突变。RNA-seq 分析表明，横纹肌肉瘤成分表达了各种与肌肉发育相关的基因，而癌性成分则没有；并且两个成分之间的基因表达总体上完全不同。我们的研究表明，在大多数情况下，PCS 的两个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有益。
