Personalised Medicine

Personalised Medicine, also often termed as Precision Medicine, is a form of medicine that uses information about a person's genes, proteins, and environment profile to prevent, diagnose, and treat disease.

However, it does not literally refer to the creation of a drug or medication that is unique to a specific patient, but the ability to classify individuals into subpopulations that differ in their susceptibility to particular disease, in the biology or prognosis of those diseases they may develop, or in their response to a specific treatment.

The goal of Personalised Medicine is to target the RIGHT treatment to the RIGHT patients at the RIGHT time. Personalised Medicine adds to, and does not replace, good medical practice. However, Personalised Medicine is not equally applicable to all diseases.

Tan Tock Seng Hospital recognises that Personalised Medicine is playing an increasingly important role in clinical practice. Therefore, the Personalised Medicine Service was established in June 2015 to provide genetic testing services and individualised treatment.

The Service has three focus areas:

Pharmacogenomics

Pharmacogenomics uses genetics and genomics tools to study drug response due to genetic factors and makes a prediction of your response to specific medications and susceptibility to toxicity and adverse effects.
Clinical Genomics

This aim of this service is to use genomics to guide treatment of cancers and complex chronic diseases. The management of some conditions can be optimised with a variety of laboratory tests, though the range of tests is small, the number is ever-increasing. Personalised Medicine also has the potential to be applied to the management of chronic diseases such as ischaemic heart disease, asthma, diabetes, and arthritis.
Rare Disease

This section employs modern genomics to diagnose patients suffering from diseases that yielded no definite diagnosis with conventional tests. Modern sequencing technology allows up to 25% of these patients to be diagnosed (Yang Y, Muzny DM, Reid JG, et al. N Engl J Med 2013; 369:1502-11). However, in spite of a diagnosis, treatment may not be available.

Genetic Counselling

During the genetic counselling session, our genetic counsellor will:

Compile a comprehensive picture of your family tree
Analyse genetic risks for certain diseases or cancer
Discuss what test are available and whether genetic testing might be right for you
Explain the results of genetic tests and what they mean for you and your family
Provide guidance and emotional support to help you decide what to do next

Some genetic conditions may need specialist care and management involving further appointments with other specialists. This is more likely to be true for the inheritable cancer syndromes. Currently, TTSH genetic counselling service is open to referrals from clinicians, mainly from Oncologists. We also accept referral from non-oncologist physicians such as Neurologists and Cardiologists.

Facilities

MDL provides a centralized platform to support genomics and pharmacogenomics from research to clinical practice. Our core facilities support sample processing, nucleic acid extraction, bio-banking, genotyping and next generation sequencing among other specialized services. The research service includes consultation on study design, informed consent, data collection and assistance with manuscript and grant preparation. These enable the exploration of the relationships among genetic variant, disease susceptibility and variable drug responses. Research services are offered through fee-of-service as well as collaborative mode.

Test and Service Offer

Pharmacogenetics
Test Description	Indication	Turnaround Time	Specimen Type & Requirement
CYP2C19 Genotyping	To predict anticoagulation response to clopidogrel and other drugs that are modified by CYP2C19.	1-3	Whole blood (EDTA, 3ml), 2 tubes
CYP3A5 Genotyping	To predict dose requirements for tacrolimus and other drugs that are modified by CYP3A5.
HLA-B*1502 Genotyping	To identify individuals with increased risk for a hypersensitivity reaction to carbamazepine.
TPMT and NUDT15 Genotyping	To predict toxicity to thiopurines.
Warfarin Genotyping	To determine the optimal initial dose of warfarin based on CYP2C9 and VKORC1 genotypes.
CYP2D6 Genotyping	To identify individuals who should avoid or have different dosing of medications metabolized by CYP2D6.	7-10
Oncology
BCR-ABL1 p210 Fusion Transcript Analysis	To monitor response to therapy in chronic myeloid leukemia patients who have the BCR-ABL p210 fusion form (e13/a2 or e14/a2).	7-10	Whole blood or bone marrow (EDTA, 3ml), 2 tubes Specimen must reach MDL within 72 hours of blood draw
CALR Exon 9 Mutation Detection	To aid in the distinction between reactive thrombocytosis and/or leukocytosis versus a myeloproliferative neoplasm (MPN).	5-7	Whole blood or bone marrow (EDTA, 3ml), 2 tubes
JAK2 V617F Mutation Detection	To aid the diagnosis of bone marrow disorders. (This test does not differentiate between heterozygous and homozygous status.)	5-7
JAK2 Exon 12/13 HRM Mutation Analysis	To aid the diagnosis of bone marrow disorders. (JAK2 exons 12 and 13 testing should be performed in JAK2 V617F negative individuals.)	7-10
JAK2 V617F, CALR Exon 9 and MPL Exon 10 Mutation Detection	To aid the diagnosis of bone marrow disorders.	7-10
MPL Exon 10 Mutation Analysis	To aid the diagnosis of bone marrow disorders.	5-7
Liquid biopsy for solid tumors	An alternative to invasive tissue biopsies to detect cancer causing gene mutations for cancer diagnosis and treatment selection. (Send out test)	7-10	Whole blood (STRECK), 2 tubes
EGFR T790M and C797S Mutation Analysis	This droplet digital PCR assay tests for the presence and allelic context (cis/trans) of EGFR T790M and C797S mutations to determine sensitivity to combination therapies. The limit of detection (LOD) of this assay has been determined at 0.5% fractional abundance. For plasma based detection, the LOD is influenced by the amount of cfDNA in the blood.	3-5	Whole blood (STRECK), 2 tubes
Hereditary disease and disorder (Send out test)
NOTCH3 Mutation Analysis*	To aid in the diagnosis of CADASIL.	10 to 14 working days	Whole blood (EDTA, 3ml), 2 tubes
Multiple Cancers panels* (Breast, Ovarian, Colon, Gastric, Pancreas, Prostate)	To detect specific genetic mutations for targeted cancer treatment or evaluate individuals with family history suggestive of predisposition to cancers. *Sponsorship for testing available for Breast, Ovarian, Pancreas or Prostate cancers***	10-14
Cardiology*	To assist with risk assessment and predictive testing of at-risk family members for Bruguda, prolonged QT syndromes or cardiomyopathy.	10-14
Whole exome sequencing*	To identify a molecular diagnosis in individuals with known or suspected genetic disorders for targeted management, risk assessment or reproductive decision making.	20-40
Others
DNA extraction	Sample processing	1-2	Whole blood (EDTA, 1-3ml)
RNA extraction	Sample processing	1-2	Whole blood (EDTA, Paxgene, 1-3ml)
Targeted sequencing*(research service only)	To detect specific variant(s) *Must be pre-arranged.*	20-40	Whole blood (EDTA, 3ml), 2 tubes
Gastroclear	This screening test evaluates the expression of 11 circulating human miRNAs associated with gastric cancer and 1 reference miRNA. It should be used in conjunction with gastroscopy to detect stomach cancer. Test is available in TTSH Health Enrichment Centre (HEC) & Gastroenterology and Hepatology.	7-10	Whole Blood (SST, 6ml), 1 tube Please hand deliver samples in cold to MDL within 2 hours after blood collection. Sample receipt timing: 8.30am – 4.30pm on Weekdays only.

* Consent required

Biorepository and Normal Controls

MDL provides TTSH investigators with repository and lab services including sample receipt and accessioning, processing and quality control, and long-term storage in ultralow freezers and liquid nitrogen tanks in a secured and 24 hour monitored environment. The team also provides end-to-end support of the biobanking process, including broad future-use sampling, assay-specific optimization, cold-chain logistics, regulatory compliance and grant budgeting.

This resource has established the TTSH normal control biobank of more than 2500 samples of healthy volunteers aged between 21-77, almost all donated generously by our staff. This cohort includes Chinese, Malay and Indian who have provided blood samples, demographic and health information for future research. It serves as a resource for health related research to improve the prevention, diagnosis and treatment of a wide range of diseases. This biobank enhances our strength as a research institution and has enabled the initiation of multiple new projects.