scholarly journals Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer

2021 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Xiaotong Li ◽  
Matthew Tucker ◽  
Shantao Li ◽  
Xinmeng Jasmine Mu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Personalized Medicine ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Advanced Prostate Cancer ◽  
Genomic Data ◽  
Tumor Board ◽  
Combined Modality Treatment ◽  
Whole Genome ◽  
Durable Response

Abstract Purpose Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain. Patient and methods We present a case of whole-genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available. Results We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient’s cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging. Conclusion We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.

scholarly journals Identifying Aspects of Public Attitudes Toward Whole Genome Sequencing to Inform the Integration of Genomics into Care

2021 ◽  
pp. 1-12
Author(s):  
Holly Etchegary ◽  
Daryl Pullman ◽  
Charlene Simmonds ◽  
Zoha Rabie ◽  
Proton Rahman
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Online Survey ◽  
Public Attitudes ◽  
Genetic Counselor ◽  
Genomic Medicine ◽  
Genomic Data ◽  
Whole Genome ◽  
The Public ◽  
Genomic Test

<b><i>Introduction:</i></b> The growth of global sequencing initiatives and commercial genomic test offerings suggests the public will increasingly be confronted with decisions about sequencing. Understanding public attitudes can assist efforts to integrate sequencing into care and inform the development of public education and outreach strategies. <b><i>Methods:</i></b> A 48-item online survey was advertised on Facebook in Eastern Canada and hosted on SurveyMonkey in late 2018. The survey measured public interest in whole genome sequencing and attitudes toward various aspects of sequencing using vignettes, scaled, and open-ended items. <b><i>Results:</i></b> While interest in sequencing was high, critical attitudes were observed. In particular, items measuring features of patient control and choice regarding genomic data were strongly endorsed by respondents. Majority wanted to specify upfront how their data could be used, retain the ability to withdraw their sample at a later date, sign a written consent form, and speak to a genetic counselor prior to sequencing. Concerns about privacy and unauthorized access to data were frequently observed. Education level was the sociodemographic variable most often related to attitude statements such that those with higher levels of education generally displayed more critical attitudes. <b><i>Conclusions:</i></b> Attitudes identified here could be used to inform the development of implementation strategies for genomic medicine. Findings suggest health systems must address patient concerns about privacy, consent practices, and the strong desire to control what happens to their genomic data through public outreach and education. Specific oversight procedures and policies that are clearly communicated to the public will be required.

scholarly journals Rapid in-country sequencing of whole virus genomes to inform rabies elimination programmes

2020 ◽  
Vol 5 ◽  
pp. 3 ◽  
Author(s):  
Kirstyn Brunker ◽  
Gurdeep Jaswant ◽  
S.M. Thumbi ◽  
Kennedy Lushasi ◽  
Ahmed Lugelo ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Data ◽  
Genomic Research ◽  
Whole Genome ◽  
Middle Income ◽  
Endemic Disease ◽  
Middle Income Countries ◽  
Virus Genomes ◽  
Low And Middle Income

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries.

Using whole-genome sequencing to implicate the androgen receptor as the predominant driver of DNA breakpoints and fusion events in prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 67-67 ◽  
Author(s):  
Niall Corcoran ◽  
Geoff Macintyre ◽  
Matthew Hong ◽  
Clare Slogget ◽  
Haroon Naeem ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Receptor Binding ◽  
Binding Sites ◽  
Whole Genome ◽  
Structural Rearrangements ◽  
Novel Gene ◽  
Close Proximity

67 Background: Structural rearrangements in cancers genomes have the potential to disrupt normal gene function and result in a selective growth advantage, either by inactivating tumour suppressors or creating novel gene fusions with oncogenic gain-of-function. Specific fusion genes identified to date are found in particular tumor types rather than being present in all cancers suggesting there are tissue-specific mechanisms underlying these events. The most well-known fusion event in prostate cancer is TMPRSS2-ERG. Recent studies have suggested that androgen receptor may play a role in the formation of TMPRSS2-ERG fusions, bringing the two loci in close proximity in the nucleus and facilitating DNA strand break and repair along with AR associated enzymes. Methods: To explore this mechanism more comprehensively, we performed whole-genome sequencing of 14 prostate cancers from seven patients as well as paired whole blood controls. Results: Across the cancer genomes we identified approximately 4,500 high confidence DNA breakpoints and found that a large proportion of these breakpoints were in close proximity to curated androgen receptor binding sites. Furthermore, when we examined breakpoints in 11 other cancers from the TCGA and ICGC projects, we identified a similar association with androgen (and estrogen) receptor binding sites specifically in hormone-dependent tumour types, suggesting a role for steroid hormone receptors in the formation of cancer driving structural rearrangements. In addition, in at least one patient, the formation of a novel gene fusion contributed directly to the lethal evolution of his tumour. Conclusions: These data suggest that the androgen receptor drives genome wide breakpoints and novel fusion events in prostate cancer.

Abstract 3925: Characterization of complex chromosomal aberrations in prostate cancer from whole genome sequencing

2011 ◽  
Author(s):  
Michael F. Berger ◽  
Michael S. Lawrence ◽  
Francesca Demichelis ◽  
Yotam Drier ◽  
Kristian Cibulskis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Chromosomal Aberrations ◽  
Whole Genome

Abstract 3184: Whole genome sequencing of low-input fresh frozen prostate cancer biopsies

2012 ◽  
Author(s):  
Michelle R. Sam ◽  
Taryne Chong ◽  
Amin Zia ◽  
Emilie Lalonde ◽  
Fouad Yousif ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Low Input ◽  
Fresh Frozen
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