Intratumour heterogeneity in urologic cancers: from molecular evidence to clinical implications.
BACKGROUND
Intratumour heterogeneity (ITH) can impair the precise molecular analysis of tumours and may contribute to difficulties encountered in cancer biomarker qualification and treatment personalisation.


OBJECTIVE
This review summarises the evidence for genetic ITH in renal, bladder, and prostate carcinomas and potential strategies to address the clinical and translational research challenges arising from ITH.


METHODS
Publications that assessed ITH in the relevant urologic cancers were identified in a literature review.


RESULTS
ITH with functionally distinct tumour subclones has been identified in all three tumour types. Heterogeneity of actionable genetic changes and of prognostic biomarkers between different tumour regions in the same patient suggests limitations of single biopsy-based molecular analyses for precision medicine approaches. Evolutionary constraints may differ between patients and may allow the prediction of specific evolutionary trajectories.


CONCLUSIONS
Assessment of multiple tumour regions for precision medicine purposes, monitoring of subclonal dynamics over time, and the preferential targeting of genetic alterations located on the trunk of the phylogenetic tree of individual cancers may accelerate the development of personalised medicine strategies and improve our understanding of treatment failure.


RESULTS
Genetic alterations can be heterogeneous within urologic tumours, complicating their use as biomarkers for treatment personalisation. We present novel strategies to address these challenges.
Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK. Electronic address: marco.gerlinger@icr.ac.uk.
Marco
M
Gerlinger
Academic Urology Unit, University of Sheffield, Sheffield, South Yorkshire, UK.
James W
JW
Catto
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Torben F
TF
Orntoft
Epithelial Carcinogenesis Group, Molecular Pathology Program, CNIO (Spanish National Cancer Research Centre), Madrid, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Francisco X
FX
Real
Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Ellen C
EC
Zwarthoff
CR-UK London Research Institute, London, UK; University College London Cancer Institute, London, UK. Electronic address: charles.swanton@cancer.org.uk.
Charles
C
Swanton
D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor
Biomarker; Bladder cancer; Cancer evolution; Genetics; Personalised medicine; Prostate cancer; Renal cancer; Tumour heterogeneity