Genomics and the Healthcare Revolution

By Amanda Goh 

 

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”.