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Spatially resolved clonal copy number alterations in benign and malignant tissue.

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Erickson et al., Nature (2022)

Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.

A Systematic Review of Prostate Cancer Heterogeneity: Understanding the Clonal Ancestry of Multifocal Disease

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Erickson et al., European Urology Oncology (2021)

We review the molecular heterogeneity of PCa and assess recent efforts to profile intratumoural heterogeneity and clonal evolution. In studies of primary disease (16 studies, 4793 specimens), there is a lack of consensus regarding the monoclonal or polyclonal origin of primary PCa. There is no consistent mutation giving rise to primary PCa. Detailed clonal analysis of primary PCa has been limited by current techniques. By contrast, clonal relationships between PCa metastases and a potentiating clone have been consistently identified (19 studies, 732 specimens). Metastatic specimens demonstrate consistent truncal genomic aberrations that suggest monoclonal metastatic progenitors.

New prostate cancer grade grouping system predicts survival after radical prostatectomy

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Erickson et al., Human Pathology (2018)

Histological Gleason grading of prostate cancer has been through modifications and conjoined into a Grade Grouping system recently. The aim of this study was to determine whether the new Grade Grouping system predicts disease-specific and all-cause mortality after radical prostatectomy. We can conclude that the new Grade Grouping system is feasible in predicting prostate cancer–specific survival after radical surgical treatment. Grade Grouping offers a simpler way to interpret the predicted course of the disease to individual patients and thus may help in justifying more conservative follow-up approaches, especially in the lower Grade Group patients.

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