# Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer

Source: https://onco.cc/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/  
OnCo record `paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing several metastases from the same man showed they are genetically much more alike than metastases from different men, so one good biopsy usually represents the rest.

## Summary

Multiple tumours from men with disseminated prostate cancer were analysed by whole-exome sequencing, array comparative genomic hybridisation and RNA transcript profiling, and genomic diversity within and between individuals was compared. In contrast to the substantial heterogeneity between men, there was limited diversity among metastases within an individual: the number of somatic mutations, the burden of copy-number alterations and aberrations in known oncogenic drivers were all highly concordant, as were metrics of androgen receptor activity and cell-cycle activity. Androgen receptor activity was inversely associated with cell proliferation, while expression of Fanconi anaemia complex genes correlated with elevated cell-cycle progression, E2F1 expression and RB1 loss. Men with somatic aberrations in Fanconi anaemia complex genes or in ATM had significantly longer responses to carboplatin than men without DNA repair gene defects.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Nature Medicine
- Year: 2016
- DOI: 10.1038/nm.4053
- Authors: Kumar A, Coleman I, Morrissey C, et al.
- Findings: Limited genomic diversity among metastases within one man against substantial diversity between men.; Concordant mutation counts, copy-number burden, driver aberrations, androgen receptor activity and cell-cycle activity across a man's metastases.; Longer carboplatin response durations in men with Fanconi anaemia complex or ATM aberrations.
- What it means: It is the reason a single metastatic biopsy is defensible in this disease, where in lung and bowel cancer heterogeneity makes one sample a gamble. The caveat is that it applies to driver alterations and not to the polyclonal resistance events that appear under treatment.
- Caveats: Rapid-autopsy and research-biopsy material, so the men are not a clinic population.; Exceptions existed and the authors said so.; The carboplatin association is retrospective and in small numbers.

## Sources

- Kumar et al., Nat Med 2016: multiple metastases per man show limited within-patient and substantial between-patient genomic diversity in disseminated prostate cancer: https://doi.org/10.1038/nm.4053
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26928463/
- cBioPortal study prad_fhcrc (Fred Hutchinson, Nat Med 2016; 141 sequenced and 149 copy-number-profiled metastases from men with disseminated prostate cancer): https://www.cbioportal.org/study/summary?id=prad_fhcrc

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [ATM](https://onco.cc/targets/atm/), [RB1](https://onco.cc/targets/rb1/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/)
- terms: [Biopsy](https://onco.cc/terms/biopsy/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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