Genomic origin and intratumor heterogeneity revealed by sequencing on carcinomatous and sarcomatous components of pulmonary sarcomatoid carcinoma

Xuewen Liu, Fang Wang, Chunwei Xu, Xinru Chen, Xue Hou, Qian Li, Pansong Li, Zhi Xie, Yongdong Liu, Lianpeng Chang, Yanfang Guan, Xuchao Zhang, Ling Yang, Hui Wang, Xin Yi, Jianjun Zhang, Xuefeng Xia, Cesar Moran, Likun Chen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Pulmonary sarcomatoid carcinoma (PSC) contains carcinomatous component (CaC) and sarcomatous component (SaC). Herein, we explored the genomic origin and intratumor heterogeneity (ITH) of PSC. We collected 31 resected PSC tumors and obtained CaC and SaC by laser capture microdissection for next-generation sequencing. The majority of PSCs (97%) had component-shared alterations. Driver mutations in EGFR, KRAS, MET, PIK3CA, and EML4-ALK fusion were mostly component-shared. Twenty-seven (87%) PSCs had component-private alterations. Compared with pure lung adenocarcinoma (LUAD), adenocarcinoma component of PSC showed lower EGFR incidence. Compared with other typical sarcomas, numerous genes of SaC exhibited significant differences. CaC and SaC had equivalent and proportional tumor mutation burden (TMB), as well as PD-L1 level. Compared with LUAD, SaC had significant higher TMB and more patients with high PD-L1 expression (tumor proportion score ≥50%). PSC with lower proportion of component-shared alterations (trunk-ratio) had a prolonged disease-free survival (DFS), regardless of the influence of clinical factors. We conclude that most PSCs originate from a monoclone accompanied by genomic ITH which is a potential independent prognostic factor, and more proportion of PSCs may be beneficial from immune checkpoint inhibitors.

Original languageEnglish (US)
Pages (from-to)821-832
Number of pages12
JournalOncogene
Volume40
Issue number4
DOIs
StatePublished - Jan 28 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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