June 10, 2013 | SINGAPORE — At the recent 2013 Bio-IT World Asia
conference, scientists and clinicians discussed how they could better
coordinate their efforts in clinical genomics and “make genomic information
usable in the clinic”.
Marcel Dinger of the Garvan Institute for Medical
Research at the Kinghorn Cancer Center enthused, clinical genomics could
“revolutionize our understanding of our genetic programming”.
Starting with Basics
Professor Patrick Tan, from the Genome Institute of
Singapore and the Institute for Genome Sciences and Policy at Duke-NUS Medical
School, began the session by describing how he has used exome sequencing to
investigate the molecular mechanisms underlying various cancers endemic to
Asia.
These studies have led to the identification of new
genes and pathways implicated in tumorigenesis. For instance, Tan showed that
the cell adhesion and chromatin modification pathways contribute to gastric
cancer development. Such information may enable the identification of new drug
targets and increase treatment options for patients.
Exome sequencing data may also show how existing drugs
may be applied to new indications. Tan’s work has also revealed that peripheral
T cell and NK/T cell lymphoma may be treated with a drug already in use for
rheumatoid arthritis, and patients with cholangiocarcinoma may respond to
therapeutic strategies already in use for pancreatic ductal
adenocarcinoma.
Moving to the Clinic
Clinical genomics may be used to diagnose inherited
diseases, especially rare ones. Jimmy Lin founded the nonprofit Rare Genomics
Institute (RGI) to help children with rare genetic diseases. He described how
more than 300 million patients are afflicted by rare diseases. There are more
than 7,000 such rare diseases, but therapy is available for less than 5% of
them. Helped by an international network of collaborators, RGI performs exome
sequencing to help these patients identify their illness and seek appropriate
treatment.
Another major application is cancer genomics, which
enables the classification of cancers based on their pathological mechanisms
and thus facilitates the design of treatment regimens. One would be able to
“treat cancer by molecular stratification instead of by tissue type,” said
Dinger, who set up a clinical genomics sequencing center.
A National Effort
Taking genomics a step further, Bogi Eliasen from the
Faroe Islands’ Ministry of Health described their vision to make genomics “the
cornerstone for optimal individualized healthcare with emphasis on prevention
as well as treatment, cost effectiveness and democratic implementation”.
Eliasen is the program director of FarGen, which aims
to incorporate whole genome sequencing into healthcare for all 50,000 Faroese
people. The small size, isolation and transparency of this close-knit community
are all advantages that permit mining of their rich genetic data.
The Faroese spent eight years developing an ethical
framework, including the Biobank Act to protect individual rights. The FarGen
project now receives strong political and public support, so the public health,
administrative and education systems are integrated into the effort, as are
multiple international academic institutions.
The FarGen project is still in its pilot phase as they
optimize and implement a prototype workflow while aiming to have 1000 genomes
sequenced by this year.
A priority for both the Faroe Islands and RGI is
patient empowerment, to enable people to take responsibility for their own
health. However, it is important to manage expectations and to allow people the
right not to know.
“All in the Learning Phase”
Marcel Dinger identified decision-making as the single
biggest challenge for clinical genomics, particularly when the information
available is new or incomplete. There are many decisions to be made, ranging
from participant selection and study design to the process of data analysis to
the mode of reporting. Different groups have different goals, which adds to the
difficulty of process standardization. Also, clinical testing protocols are
subject to rigorous regulation but constantly evolve as technology
advances.
Most speakers cited cost as a major problem. Although
the cost of sequencing has decreased significantly, the subsequent
computational and manual analyses as well as data storage are time-consuming
and expensive.
To re-evaluate and improve treatment strategies, a
genotype-phenotype database that records clinical phenotypes is necessary. But
information must be obtained from the patients’ medical records, entries into
which are not standardized in terms of language, rendering analysis
difficult.
All the speakers agreed with Lin, who said that we are
“all in the learning phase”. Dinger emphasized the need for international
collaboration and engagement with other consortia to provide “strength in
numbers”. The unifying goal would be the incorporation of genomics in routine
clinical care, which he predicts would enable a shift to personal and precision
medicine and “a system that is primarily geared toward health optimization
rather than crisis management”.
Amanda Goh
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