A molecular approach integrating genomic and DNA methylation profiling for tissue of origin identification in lung-specific cancer of unknown primary

doi:10.1186/s12967-022-03362-2

	A molecular approach integrating genomic and DNA methylation profiling for tissue of origin identification in lung-specific cancer of unknown primary
	Chen, Kaiyan 1,2,3; Zhang, Fanrong 1,2,4; Yu, Xiaoqing 1,2,5; Huang, Zhiyu 1,2,3; Gong, Lei 1,2,3; Xu, Yanjun 1,2,3; Li, Hui 1,2,3; Yu, Sizhe 1,2,3; Fan, Yun 1,2,3,6
刊名	JOURNAL OF TRANSLATIONAL MEDICINE
	2022-04-05
卷号	20
关键词	Cancer with unknown primary (CUP) Multiple primary tumor Comprehensive genomic profiling (CGP) DNA methylation Machine learning Lung cancer
DOI	10.1186/s12967-022-03362-2
通讯作者	Fan, Yun(fanyun@zjcc.org.cn)
英文摘要	Background Determining the tissue of origin (TOO) is essential for managing cancer of unknown primary (CUP). In this study, we evaluated the concordance between genome profiling and DNA methylation analysis in determining TOO for lung-specific CUP and assessed their performance by comparing the clinical responses and survival outcomes of patients predicted with multiple primary or with metastatic cancer. Methods We started by retrospectively screening for CUP patients who presented with both intra- and extrathoracic tumors. Tumor samples from included patients were analyzed with targeted sequencing with a 520-gene panel and targeted bisulfite sequencing. TOO inferences were made in parallel via an algorithm using genome profiles and time interval between tumors and via machine learning-based classification of DNA methylation profiles. Results Four hundred patients were screened retrospectively. Excluding patients definitively diagnosed with conventional diagnostic work-up or without available samples, 16 CUP patients were included. Both molecular approaches alone enabled inference of clonality for all analyzed patients. Genome profile enabled TOO inference for 43.8% (7/16) patients, and the percentage rose to 68.8% (11/16) after considering inter-tumor time lag. On the other hand, DNA methylation analysis was conclusive for TOO prediction for 100% (14/14) patients with available samples. The two approaches gave 100% (9/9) concordant inferences regarding clonality and TOO identity. Moreover, patients predicted with metastatic disease showed significantly shorter overall survival than those with multiple primary tumors. Conclusions Genome and DNA methylation profiling have shown promise as individual analysis for TOO identification. This study demonstrated the feasibility of incorporating the two methods and proposes an integrative scheme to facilitate diagnosing and treating lung-specific CUPs.
资助项目	Basic Public Foundation of Zhejiang Province of China[LGF18H160017]
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	BMC
WOS记录号	WOS:000778499200009
资助机构	Basic Public Foundation of Zhejiang Province of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/128687]
专题	中国科学院合肥物质科学研究院
通讯作者	Fan, Yun
作者单位	1.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou 310022, Peoples R China 2.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Peoples R China 3.Zhejiang Canc Hosp, Dept Thorac Med Oncol, Hangzhou 310022, Peoples R China 4.Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou 310022, Peoples R China 5.Zhejiang Canc Hosp, Dept Clin Trial, Hangzhou 310022, Peoples R China 6.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Med Oncol, Hangzhou 310022, Peoples R China
推荐引用方式 GB/T 7714	Chen, Kaiyan,Zhang, Fanrong,Yu, Xiaoqing,et al. A molecular approach integrating genomic and DNA methylation profiling for tissue of origin identification in lung-specific cancer of unknown primary[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2022,20.
APA	Chen, Kaiyan.,Zhang, Fanrong.,Yu, Xiaoqing.,Huang, Zhiyu.,Gong, Lei.,...&Fan, Yun.(2022).A molecular approach integrating genomic and DNA methylation profiling for tissue of origin identification in lung-specific cancer of unknown primary.JOURNAL OF TRANSLATIONAL MEDICINE,20.
MLA	Chen, Kaiyan,et al."A molecular approach integrating genomic and DNA methylation profiling for tissue of origin identification in lung-specific cancer of unknown primary".JOURNAL OF TRANSLATIONAL MEDICINE 20(2022).