Krause, Arthur; Roma, Luca; Lorber, Thomas; Dietsche, Tanja; Perrina, Valeria; Müller, David C; Lardinois, Didier; Ruiz, Christian; Savic Prince, Spasenija; Piscuoglio, Salvatore; Ng, Charlotte K. Y.; Bubendorf, Lukas (2021). Genomic evolutionary trajectory of metastatic squamous cell carcinoma of the lung. Translational lung cancer research, 10(4), pp. 1792-1803. AME Publishing 10.21037/tlcr-21-48
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Background
The extent of inter- and intratumoral genomic heterogeneity and the clonal evolution of metastatic squamous cell carcinoma of the lung (LUSC) are poorly understood. Genomic studies of LUSC are challenged by their low tumor cell content. We sought to define the genomic landscape and evolutionary trajectories of metastatic LUSC combining nuclei-flow sorting and whole exome sequencing.
Methods
Five patients with primary LUSC and six matched metastases were investigated. Tumor nuclei were sorted based on ploidy and expression of cytokeratin to enrich for tumor cells for whole exome sequencing.
Results
Flow-sorting increased the mean tumor purity from 26% (range, 12-50%) to 73% (range, 42-93%). Overall, primary LUSCs and their matched metastases shared a median of 79% (range, 67-85%) of copy number aberrations (CNAs) and 74% (range, 65-94%) of non-synonymous mutations, including in tumor suppressor genes such as TP53. Furthermore, the ploidy of the tumors remained unchanged between primary and metastasis in 4/5 patients over time. We found differences in the mutational signatures of shared mutations compared to the private mutations in the primary or metastasis.
Conclusions
Our results demonstrate a close genomic relationship between primary LUSCs and their matched metastases, suggesting late dissemination of the metastases from the primary tumors during tumor evolution.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Ng, Kiu Yan Charlotte |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2226-4477 |
Publisher: |
AME Publishing |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
24 Jan 2022 07:25 |
Last Modified: |
05 Dec 2022 16:00 |
Publisher DOI: |
10.21037/tlcr-21-48 |
PubMed ID: |
34012793 |
Uncontrolled Keywords: |
Squamous cell carcinoma flow sorting heterogeneity lung cancer metastasis tumor evolution whole exome sequencing |
BORIS DOI: |
10.48350/163429 |
URI: |
https://boris.unibe.ch/id/eprint/163429 |
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