title: Comparing nodal versus bony metastatic spread using tumour phylogenies.
abstract: The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.|Centre for Neural Engineering, 203 Bouverie St, Carlton 3053, Victoria, Australia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mangiola
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.
authors.forename: Matthew K H
authors.initials: MK
authors.lastname: Hong
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.|Centre for Neural Engineering, 203 Bouverie St, Carlton 3053, Victoria, Australia.
authors.forename: Marek
authors.initials: M
authors.lastname: Cmero
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Kurganovs
authors.affiliation: TissuPath Specialist Pathology, Mount Waverley 3149, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.|The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Costello
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.|The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
authors.forename: Niall M
authors.initials: NM
authors.lastname: Corcoran
authors.affiliation: Centre for Neural Engineering, 203 Bouverie St, Carlton 3053, Victoria, Australia.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Macintyre
authors.affiliation: Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.|The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens