TY - JOUR
T1 - Genomic origin and intratumor heterogeneity revealed by sequencing on carcinomatous and sarcomatous components of pulmonary sarcomatoid carcinoma
AU - Liu, Xuewen
AU - Wang, Fang
AU - Xu, Chunwei
AU - Chen, Xinru
AU - Hou, Xue
AU - Li, Qian
AU - Li, Pansong
AU - Xie, Zhi
AU - Liu, Yongdong
AU - Chang, Lianpeng
AU - Guan, Yanfang
AU - Zhang, Xuchao
AU - Yang, Ling
AU - Wang, Hui
AU - Yi, Xin
AU - Zhang, Jianjun
AU - Xia, Xuefeng
AU - Moran, Cesar
AU - Chen, Likun
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/1/28
Y1 - 2021/1/28
N2 - 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.
AB - 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.
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U2 - 10.1038/s41388-020-01573-9
DO - 10.1038/s41388-020-01573-9
M3 - Article
C2 - 33273725
AN - SCOPUS:85097009448
SN - 0950-9232
VL - 40
SP - 821
EP - 832
JO - Oncogene
JF - Oncogene
IS - 4
ER -