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Frequent clonal relations between metastases and non-index prostate cancer lesions
Jeroen Kneppers, … , Wilbert Zwart, Andries M. Bergman
Jeroen Kneppers, … , Wilbert Zwart, Andries M. Bergman
Published January 24, 2019
Citation Information: JCI Insight. 2019;4(2):e124756. https://doi.org/10.1172/jci.insight.124756.
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Research Article Genetics Oncology

Frequent clonal relations between metastases and non-index prostate cancer lesions

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Abstract

Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. In this study, we compared copy number aberration profiles of primary prostate cancer lesions with matching pelvic lymph node metastases of 30 patients to establish clonality between a lymph node metastasis and multiple primary lesions within the same patient. Interestingly, in 23.3% of the cases, the regional metastasis was not clonally linked to the index primary lesion. These findings suggest that focal ablation of only the index lesion is potentially an undertreatment of a significant proportion of prostate cancer patients.

Authors

Jeroen Kneppers, Oscar Krijgsman, Monique Melis, Jeroen de Jong, Daniel S. Peeper, Elise Bekers, Henk G. van der Poel, Wilbert Zwart, Andries M. Bergman

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Figure 3

Clonality assessment of PCa lesions and LN metastases.

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Clonality assessment of PCa lesions and LN metastases.
(A) Density plot ...
(A) Density plot of log likelihood ratio (LR) of 3 pair groups: reference distribution, P1–N pairs, and P2–n–N pairs. A box plot representation of the density plot is shown in the corner. Dotted line represents LR P value of 0.01, which is considered significant. (B) Intrapatient CNA heatmap comparison of P1 and N, indicating that 23.3% of LN metastases are not clonally related to the primary index lesion. Two CNA heatmaps from 2 patients are shown as examples. Patient 3 shows no clonality between P1 and N. Patient 13 shows clonality between P1 and N based on identical breakpoints in genomes.

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