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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 1

Case study of patient 11.

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Case study of patient 11.
(A) Schematic representation of a prostate wit...
(A) Schematic representation of a prostate with multiple primary lesions (P) and a pelvic LN metastasis (N). (B) Example CNA profiles showing different SGR features in the index lesion P1, other primary lesion P2, and LN metastasis N. Breakpoint features are shared between N and P1. (C) H&E staining of the FFPE whole-mount prostatectomy and an LN metastasis of patient 11. The index lesion P1 and 2 other primary lesions (P2 and P3) as well as the LN metastasis are indicated. Marks in P1 where 3 cores were taken are indicated. (D) Selected CNA profiles of patient 11 acquired by LC-WGS and processed with QDNAseq (see Methods). Black dots represent log2 ratio values in bins of 30 kb; red lines represent segmented log2 ratio values. (E) Pearson correlation heatmap of segmented CGHcall (15) values of all isolated tumors of patient 11. (F) Principal component analysis plot of segmented CGHcall values of P1, P2–n, and N.

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