Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity.

  title={Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity.},
  author={Marthe L{\o}vf and Sen Zhao and Ulrika Axcrona and Bjarne Johannessen and Anne Cathrine Bakken and Kristina T Carm and Andreas M. Hoff and Ola Myklebost and Leonardo A. Meza-Zepeda and Agnes Kathrine Lie and Karol Axcrona and Ragnhild A. Lothe and Rolf I. Skotheim},
  journal={European urology},
  volume={75 3},

Expressed prognostic biomarkers for primary prostate cancer independent of multifocality and transcriptome heterogeneity.

An extensive heterogeneity in multifocal prostate cancer is confirmed at the gene expression level, with 16 genes associated with biochemical recurrence in a separately published study nominated as biomarkers with prognostic value regardless of which malignant focus is sampled.

Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer

The level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.

Proteogenomic heterogeneity of localized human prostate cancer progression

This study revealed molecular networks with remarkably convergent alterations across tumor sites and patients, but it also exposed a diversity of network effects: it could not identify a single sub-network that was perturbed in all high-grade tumor regions.

Intratumoral heterogeneity and genetic characteristics of prostate cancer

This study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden, variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures.

Genomics of lethal prostate cancer at diagnosis and castration resistance

The genomics of diagnostic prostatic biopsies acquired from men who develop mCRPC differ from those of the nonlethal primary prostatic cancers, with RB1/TP53/AR aberrations are enriched in later stages, but the prevalence of DDR defects in diagnostic samples is similar to m CRPC.

Genomic and phenotypic heterogeneity in prostate cancer

This finding demonstrates that multiple genomically and phenotypically distinct primary prostate cancers can be present in an individual patient, and summarizes the manifestations of inter-tumoural and intra-t tumoural heterogeneity in primary and metastatic prostate cancer.

The somatic clinico-genomics of localized, non-indolent prostate cancer

A “state of the field” overview of prostate cancer genomics is provided, with particular focus on localized, non-indolent disease, and discusses recurrent somatic aberrations, across multiple mutational classes, which characterize this disease state.

Genomic Profiling of Prostate Cancer: An Updated Review

Emerging evidence for genomic profiling of prostate cancer is reviewed, especially focusing on associations between genomic alteration and clinical outcome, liquid biopsy, and actionable molecular alterations.

Prostate epithelial genes define therapy-relevant prostate cancer molecular subtype

PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents, and four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics are proposed.

Distinct Genomic Alterations in Prostate Tumors Derived from African American Men

Analysis of somatic mutations in 39 genes using deeper next-generation sequencing finds ZMYM3 is the most frequently mutated gene in AA prostate cancer, and deletions of MAP3K7, BNIP3L, RB1, and NEIL3, and gain of MYC appear to be distinct somatically acquired genetic alterations that may contribute to more aggressive prostate cancer in AA/black men.



Spatial genomic heterogeneity within localized, multifocal prostate cancer

A new recurrent amplification of MYCL is identified and validated, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation, and this data represents the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome.

Substantial inter-individual and limited intra-individual genomic diversity among tumors from men with metastatic prostate cancer

Analysis of multiple tumors from men with disseminated prostate cancer indicates that evaluating a single metastasis provides a reasonable assessment of the major oncogenic driver alterations that are present in disseminated tumors within an individual, and thus may be useful for selecting treatments on the basis of predicted molecular vulnerabilities.

Genomic hallmarks of localized, non-indolent prostate cancer

It is suggested that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates and numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberration outperformed well-described prognostic biomarkers.

Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men, demonstrating the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis.

The long tail of oncogenic drivers in prostate cancer

A new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway are identified.