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Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.

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Human genetic data access agreement for institutions

This agreement governs the terms on which access will be granted to the genotype data generated by the Prostate Cancer Research Center, University of Tampere.In signing this agreement, You agree to be bound by the terms and conditions of access set out in this agreement.For the sake of clarity, the terms of access set out in this agreement apply both to the User and the User’s Institution (as defined below). User Institution and User are referred to within the agreement as “You”.Definitions:PCRC means the Prostate Cancer Research Center, a research institute operating under the University of Tampere, Finland.Data means any human genetic or clinical data obtained from the Prostate Cancer Research Center.Data Subject means a person to whom Data refers and who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto.User means a researcher whose User Institution has previously completed this Data Access Agreement and has received acknowledgement of its acceptance.User Institution means the organization at which the User is employed, affiliated or enrolled.?Terms and Conditions:In signing this Agreement:You agree to use the Data only for the advancement of medical research, according to the consent obtained from sample donors.You agree to preserve, at all times, the confidentiality of information and Data pertaining to Data Subjects. In particular, You undertake not to use, or attempt to use the Data to compromise or otherwise infringe the confidentiality of information on Data Subjects and their right to privacy.You agree not to transfer or disclose the Data, in whole or part, or any identifiable material derived from the Data, to others, except as necessary for data/safety monitoring or programme management. Should You wish to share the Data with a collaborator in the same Institution, the third party must make a separate application for access to the Data.You agree to use the data for the approved purpose and project described in your application; use of the data for a new purpose or project will require a new application and approval.You accept that Data will be reissued from time to time, with suitable versioning. If the reissue is at the request of sample donors and/or other ethical scrutiny, You will destroy earlier versions of the Data.You agree to acknowledge in any work based in whole or part on the Data, the published paper from which the Data derives, the version of the data, and the role of PCRC and the relevant primary collectors and their funders.You accept that the PCRC, the original data creators, depositors or copyright holders, or the funders of the Data or any part of the Data supplied:bear no legal responsibility for the accuracy or comprehensiveness of the Data; andaccept no liability for indirect, consequential, or incidental, damages or losses arising from use of the Data, or from the unavailability of, or break in access to, the Data for whatever reason.You understand and acknowledge that the Data is protected by copyright and other intellectual property rights, and that duplication, except as reasonably required to carry out Your research with the Data, or sale of all or part of the Data on any media is not permitted.You recognise that nothing in this agreement shall operate to transfer to the User Institution any intellectual property rights relating to the Data. The User Institution has the right to develop intellectual property based on comparisons with their own data.You accept that this agreement will terminate immediately upon any breach of this agreement by You and You will be required to destroy any Data held.You accept that it may be necessary for PCRC or its appointed agent to alter the terms of this agreement from time to time in order to address new concerns. In this event, IBT or its appointed agent will contact You to inform You of any changes and You agree that Your continued use of the Data shall be dependent on the parties entering into a new version of the Agreement.You accept that the Data is protected by and subject to international laws, including but not limited to the EU Data Protection Directive 1995 (officially Directive 95/46/EC), and that You are responsible for ensuring compliance with any such applicable law. The Data Access Committee reserves the right to request and inspect data security and management documentation to ensure the adequacy of data protection measures in countries that have no national laws comparable to that which pertain in the European Economic Area.This agreement shall be construed, interpreted and governed by the laws of Finland and shall be subject to the non-exclusive jurisdiction of the Finnish courts.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001001659 Other
ID File Type Size Located in
EGAF00000976692 fq.gz 4.0 GB
EGAF00000976693 fq.gz 4.0 GB
EGAF00000976694 fq.gz 3.8 GB
EGAF00000976695 fq.gz 3.9 GB
EGAF00000976696 fq.gz 4.1 GB
EGAF00000976697 fq.gz 4.2 GB
EGAF00000976698 fq.gz 3.7 GB
EGAF00000976699 fq.gz 3.8 GB
EGAF00000976700 fq.gz 4.2 GB
EGAF00000976701 fq.gz 4.2 GB
EGAF00000976702 fq.gz 4.3 GB
EGAF00000976703 fq.gz 4.2 GB
EGAF00000976704 fq.gz 4.4 GB
EGAF00000976705 fq.gz 4.4 GB
14 Files (57.2 GB)