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

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.

[1]  Natalie S. Fox,et al.  The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression , 2018, Cell.

[2]  Yi Mi Wu,et al.  The long tail of oncogenic drivers in prostate cancer , 2018, Nature Genetics.

[3]  L. Matthews,et al.  Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data , 2017, PLoS genetics.

[4]  H. G. van der Poel,et al.  EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. , 2017, European urology.

[5]  N. McGranahan,et al.  Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future , 2017, Cell.

[6]  F. Markowetz,et al.  How Subclonal Modeling Is Changing the Metastatic Paradigm , 2016, Clinical Cancer Research.

[7]  A. Costello,et al.  Comparing nodal versus bony metastatic spread using tumour phylogenies , 2016, Scientific Reports.

[8]  A. Jemal,et al.  Prostate cancer incidence in 43 populations worldwide: An analysis of time trends overall and by age group , 2016, International journal of cancer.

[9]  Michael Kerger,et al.  Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer , 2015, Nature Communications.

[10]  M. Nykter,et al.  The Evolutionary History of Lethal Metastatic Prostate Cancer , 2015, Nature.

[11]  M. Rubin,et al.  Genomic rearrangements in prostate cancer , 2015, Current opinion in urology.

[12]  Pieter Wesseling,et al.  DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly , 2014, Genome research.

[13]  W. Isaacs,et al.  Tracking the clonal origin of lethal prostate cancer. , 2013, The Journal of clinical investigation.

[14]  P. Scardino,et al.  Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. , 2012, European urology.

[15]  Adam B. Olshen,et al.  Clonality: an R package for testing clonal relatedness of two tumors from the same patient based on their genomic profiles , 2011, Bioinform..

[16]  F. Algaba,et al.  Impact of prostate cancer multifocality on its biology and treatment. , 2010, Journal of endourology.

[17]  Jun Luo,et al.  Copy Number Analysis Indicates Monoclonal Origin of Lethal Metastatic Prostate Cancer , 2009, Nature Medicine.

[18]  M. Wigler,et al.  Circular binary segmentation for the analysis of array-based DNA copy number data. , 2004, Biostatistics.

[19]  T. Stamey,et al.  Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens. , 2002, Urology.

[20]  Mark Emberton,et al.  New and Established Technology in Focal Ablation of the Prostate: A Systematic Review. , 2017, European urology.

[21]  Wessel N. van Wieringen,et al.  CGHcall: Calling aberrations for array CGH tumor profiles. , 2008 .

[22]  Julian Savulescu.  No consent should be needed for using leftover body material for scientific purposes. Against. , 2002, BMJ.

[23]  R. Jenkins,et al.  Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by fluorescence in situ hybridization. , 1997, The Journal of urology.

[24]  Heng Li,et al.  BIOINFORMATICS ORIGINAL PAPER , 2022 .