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Mutational landscape of paired primary and synchronous metastatic lymph node in chemotherapy naive gallbladder cancer

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Abstract

Background

Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships in gallbladder cancer (GBC) is limited.

Methods

We performed whole exome sequencing for 5 patients with primary tumor, metastatic lymph node (LNM) and corresponding normal tissue. Mutations, mutation signatures and copy number variations were analyzed with state-of-art bioinformatics methods. Phylogenetic tree was also generated to infer metastatic pattern.

Results

Five driver mutations were detected in these patients. Among which, TP53 was the only shared mutation between primary tumor and LNM. Although tumor mutational burden was comparable between primary tumor and LNM, higher mutation burden was observed in LNM of one patient. Copy number variations (CNVs) burden was higher in LNM than their primary tumor. Phylogenetic analysis indicated both linear and parallel progression of metastasis exist in these patients. TP53 mutation and CNVs were homogenously between primary tumor and LNM.

Conclusions

High consistence of genetic landscape were shown between primary tumor and LNM in GBC. However, heterogenicity still exist between primary tumor and LNM in particular patients in term of driver mutation, TMB and CNV burden. Phylogenetic analysis indicated both Linear and parallel progression of metastasis were exist among these patients.

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Data availability

All raw data is available, and is ready to share.

Code availability

All the software used in this manuscript is available online, and there is no custom code.

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Author notes

  1. Boqiang Fan and Xianfeng Xu have contributed equally to this article.

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, Jiangsu Province, China

    Boqiang Fan

  2. Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China

    Xianfeng Xu

  3. Key Laboratory of Liver Transplantation, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Chinese Academy of Medical Sciences, Nanjing, Jiangsu Province, China

    Xuehao Wang

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  1. Boqiang Fan
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Contributions

XFX and BQF performed WES, critical data analyses, interpretation of results and wrote the manuscript. XFX performed DNA extraction, analyzed the data and carried out statistical analyses. BQF contributed samples and analyzed clinical data. BQF and XHW designed, implemented the study, wrote and critically reviewed the manuscript. This is to confirm that all authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuehao Wang.

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Since this is an retrospective diagnostic study, no previous agreement from our Ethical Committee was obtained.

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Fan, B., Xu, X. & Wang, X. Mutational landscape of paired primary and synchronous metastatic lymph node in chemotherapy naive gallbladder cancer. Mol Biol Rep 49, 1295–1301 (2022). https://doi.org/10.1007/s11033-021-06957-y

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  • DOI: https://doi.org/10.1007/s11033-021-06957-y

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