Genomic and transcriptomic profiling of combined small-cell lung cancer through microdissection: unveiling the transformational pathway of mixed subtype.

Autor: Ma W; Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China., Zhou T; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China., Song M; Geneplus-Beijing Institute, Beijing, 102206, People's Republic of China., Liu J; Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China., Chen G; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China., Zhan J; Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China., Ji L; Geneplus-Beijing Institute, Beijing, 102206, People's Republic of China., Luo F; Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China., Gao X; Geneplus-Beijing Institute, Beijing, 102206, People's Republic of China., Li P; Geneplus-Beijing Institute, Beijing, 102206, People's Republic of China., Xia X; Geneplus-Beijing Institute, Beijing, 102206, People's Republic of China., Huang Y; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China. huangyan@sysucc.org.cn., Zhang L; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China. zhangli@sysucc.org.cn.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2024 Feb 21; Vol. 22 (1), pp. 189. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1186/s12967-024-04968-4
Abstrakt: Background: Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive.
Methods: Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases.
Results: We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion.
Conclusions: Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.
(© 2024. The Author(s).)
Databáze: MEDLINE
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