Utility of whole exome sequencing analysis in differentiating intrapulmonary metastatic multiple ground-glass nodules (GGNs) from multiple primary GGNs.

Content Provider	Europe PMC
Author	Zhou, Dong Liu, Quan-Xing Li, Man-yuan Hou, Bin Yang, Gui-xue Lu, Xiao Zheng, Hong Jiang, Li Dai, Ji-Gang
Abstract	PurposeClinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear.Experimental designSixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs.ResultsA total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort.ConclusionsOur findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10147-022-02134-8.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9023437&blobtype=pdf
ISSN	13419625
Journal	International Journal of Clinical Oncology [Int J Clin Oncol]
Volume Number	27
DOI	10.1007/s10147-022-02134-8
PubMed Central reference number	PMC9023437
Issue Number	5
PubMed reference number	35171361
e-ISSN	14377772
Language	English
Publisher	Springer Nature Singapore
Publisher Date	2022-02-16
Publisher Place	Singapore
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022
Subject Keyword	Lung cancer Multiple ground-glass nodule (GGN) Whole exome sequencing (WES) Clone evolution analysis
Content Type	Text
Resource Type	Article
Subject	Hematology Surgery Oncology