Next Article in Journal
Dysregulation of Rho GTPases in Human Cancers
Next Article in Special Issue
Applications of Artificial Intelligence to Prostate Multiparametric MRI (mpMRI): Current and Emerging Trends
Previous Article in Journal
Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy
Previous Article in Special Issue
KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells
Open AccessArticle

The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis

1
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
2
St. Vincent’s Clinical School, University of New South Wales, Sydney, Randwick, NSW 2031, Australia
3
Kinghorn Cancer Centre, Department of Medical Oncology, St. Vincent’s Hospital, Darlinghurst, NSW 2010, Australia
4
Central Clinical School, University of Sydney, Sydney, Camperdown, NSW 2050, Australia
5
Australian Prostate Cancer Research Centre Epworth, Richmond, VIC 3121, Australia
6
Department of Surgery, University of Melbourne, Melbourne, VIC 3010, Australia
7
Division of Urology, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
8
Department of Orthopedic Surgery, Scripps Clinic, La Jolla, CA 92037, USA.
9
Orthopedic Oncology Program, Scripps MD Anderson Cancer Center, La Jolla, CA 92037, USA
10
The Centre for Proteomic and Genomic Research, Cape Town 7925, South Africa
11
Department of Urology, St. Vincent’s Hospital, Darlinghurst, NSW 2010, Australia
12
Department of Urology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA
13
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Randwick, NSW 2031, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(5), 1178; https://doi.org/10.3390/cancers12051178
Received: 18 March 2020 / Revised: 21 April 2020 / Accepted: 28 April 2020 / Published: 7 May 2020
(This article belongs to the Collection Urological Cancer)
Background: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment. Methods: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain. Results: Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (LRP1B, CDK12, MLH1) and one patient had germline and somatic BRCA2 alterations. Conclusions: Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual’s molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease. View Full-Text
Keywords: prostate cancer; precision medicine; whole genome sequencing; optical mapping; therapy prostate cancer; precision medicine; whole genome sequencing; optical mapping; therapy
Show Figures

Figure 1

  • Supplementary File 1:

    ZIP-Document (ZIP, 540 KB)

  • Externally hosted supplementary file 1
    Doi: 10.25833/7wqs-gb12
    Description: The WGM data is available at the following DOI: 10.25833/7wqs-gb12
MDPI and ACS Style

Crumbaker, M.; Chan, E.K.F.; Gong, T.; Corcoran, N.; Jaratlerdsiri, W.; Lyons, R.J.; Haynes, A.-M.; Kulidjian, A.A.; Kalsbeek, A.M.F.; Petersen, D.C.; Stricker, P.D.; Jamieson, C.A.M.; Croucher, P.I.; Hovens, C.M.; Joshua, A.M.; Hayes, V.M. The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis. Cancers 2020, 12, 1178.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop