Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, No.185, Juqian Road, Tianning District, Changzhou City, Jiangsu Province, People's Republic of China.
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People's Republic of China.
Int J Clin Oncol. 2019 Sep;24(9):1061-1068. doi: 10.1007/s10147-019-01454-6. Epub 2019 May 7.
Pulmonary sarcomatoid carcinoma (PSC) is a group of rare tumors with the presence of both cancerous and sarcoma components in tumor. In this study, we explore their cancer genomic background and the relationship with clinical prognosis.
A cohort of 32 PSC patients were retrospectively collected from the First People's Hospital of Changzhou between 2005 and 2016. Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 32 PSC tumors.
EGFR (28%), KRAS (22%), and MET (16%) are the most commonly mutated oncogenes, while the top mutated tumor suppressor genes are TP53 (69%) and RB1 (25%). The majority of EGFR mutations are rare mutations, some of which have not been reported before. Moreover, 4 out of 6 MET alterations are exon 14 skipping, far more frequent than in NSCLC. Interestingly, ARID1A was found to be co-mutated with TP53 at all times. The tumor mutation burden (TMB) is ranging from 3.3 to 52.2 per megabase (MB) with a median of 11.7 per MB and 13 patients have more than 20 mutations per MB. Patients mutated in BRCA2, KMT2B, SMARCA4 or TSC2 have significantly higher TMB compared to patients with wide-type genes.
Our study characterizes the genetic background of Chinese PSC patients and demonstrates the importance of involving EGFR rare mutations and MET exon 14 skipping targeted therapies into clinical trials for treating PSC patients. High TMB are seen in about 40.6% Chinese patients with PSC, which could benefit from immune checkpoint inhibitors.
肺肉瘤样癌（PSC）是一组罕见的肿瘤，其肿瘤中既有癌性成分又有肉瘤成分。在本研究中，我们探讨了它们的癌症基因组背景及其与临床预后的关系。
回顾性收集了 2005 年至 2016 年期间常州第一人民医院的 32 例 PSC 患者。对 32 例 PSC 肿瘤进行了 416 个癌症相关基因的靶向下一代测序（NGS）。
EGFR（28%）、KRAS（22%）和 MET（16%）是最常见的突变致癌基因，而 TOP 突变的肿瘤抑制基因是 TP53（69%）和 RB1（25%）。大多数 EGFR 突变是罕见突变，其中一些以前从未报道过。此外，6 个 MET 改变中有 4 个是外显子 14 跳跃，远高于 NSCLC。有趣的是，ARID1A 始终与 TP53 共同突变。肿瘤突变负荷（TMB）范围为 3.3 至 52.2 个每兆碱基（MB），中位数为 11.7 个每 MB，有 13 例患者的每 MB 突变超过 20 个。BRCA2、KMT2B、SMARCA4 或 TSC2 突变的患者的 TMB 明显高于野生型基因的患者。
我们的研究描述了中国 PSC 患者的遗传背景，并表明将 EGFR 罕见突变和 MET 外显子 14 跳跃靶向治疗纳入治疗 PSC 患者的临床试验具有重要意义。大约 40.6%的中国 PSC 患者存在高 TMB，这可能受益于免疫检查点抑制剂。
