Personalized Genomics Will Become An Integral Part Of Customized Healthcare: Subhamoy Dastidar

Tell us about the recent trends in the genomics market. And how has COVID-19 impacted it?

Recently, there has been a significant increase in the awareness of genetic testing amongst the Indian public. The rate at which awareness has increased is due to initiatives of organizations such as ORDI (Organization for Rare Diseases in India). Events such as the clinical trial programs for Genetic diseases such as Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) have increased the awareness about genetic factors and their role in disease development and progression. With this increased awareness another important understanding is that each of us has a unique genetic composition. Therefore when Genetic changes occur and result in diseases such as Cancer, by understanding the changes that have happened we are able to get more effective treatment solutions. This is known as personalized or precision medicine. Because of increased awareness and better outcomes of using this approach, this type of genetic testing is gaining traction in India. Personalized genomics also gives insights into complex yet common disorders such as Cardiovascular Diseases and Diabetes. There are underlying genetic risk factors for such disorders which can be analyzed and help in better management. The impact of COVID-19 has been on Genomics has been increased usage of Genetic testing in the context of infectious diseases which was done on a much smaller scale prior to the pandemic.

Personalized genomics is being attributed as the future of healthcare. How do you see this?

At Lilac Insights we believe that personalized genomics will become an integral part of customized healthcare which would result in better patient outcomes. These can be broadly divided into two groups, causative genetic changes, wherein any mutation or change in the DNA in a gene results in a disease, this is the case for single-gene disorders such as Cystic Fibrosis and Sickle Cell disease.

The other type which has come to light with advances in genetic testing technology and large population based studies are, genetic risk factors for diseases. These genetic risk factors may increase the risk of an individual for developing a disease such as Diabetes and certain cardiac diseases. One interesting possible application of genomics can be in managing health during pregnancy to avoid unwanted outcomes. Often the primary reason for variations during the pregnancy is due to genetic variation between two individuals.  These variations are often hereditary in nature, passed down in the family, and thereby some women may be predisposed to certain conditions during their period of pregnancy. The impacts of these variations are therefore often unique to an individual. Some variations may have direct links to the individual’s health and sometimes to the fetus. With the advancement of medical science and genomic knowledge, these variations can be identified and categorized for every woman to avoid unwanted complications. 

In Oncology, personalized genomics is rapidly progressing in identifying the molecular signature of a tumour and thereby allowing more effective and targeted treatment based on this signature. Similarly, another key area for personalized genomics is Pharmacogenomics which can assess the ability of a patient to metabolize pharmaceutical drugs. This would help the doctor use more effective drugs in proper dosage and avoid toxicity due to poor drug metabolism.

What is the role of genetics in reproductive cancers?

Reproductive cancers include cancers of the reproductive system in men and women. The most common types include Breast, Ovarian in women and prostate and testicular cancer in men. There are two forms of reproductive cancers, one based on whether the mutation causing the cancer is inherited and the other is if it has occurred in the patient in a specific tissue. The former is known as a Germline mutation and has a high risk of recurrence, an example of the Hereditary Breast and Ovarian Cancer syndrome (HBOC). Germline mutations are present in all tissue types and not only the affected organs. The latter type of mutation is known as Somatic Mutations which occur in the specific tissue and carry a low recurrence risk. 95 per cent of endometrial cancers are somatic. Genetic testing for reproductive cancers is essential to determine which mutations or single nucleotide variation (SNVs) or copy number variations (CNVs) and gene fusions are the genetic cause for the cancer observed. Two well-known genes associated with hereditary breast and ovarian cancers are BRCA1 and BRCA2. However, several studies have shown further information can be obtained in breast and ovarian cancer cases which are negative for BRCA1/2 mutation by determining the Homologous Repair pathway status.  Homologous Repair Deficient (HRD) cancers can be treated using PARP inhibitor therapy. This represents a multimodal genetic analysis of cancers which can give a clinician more actionable insights.

What kind of assistance is provided to the patients along with the testing facilities?

Genetic counselling is a critical component in every genetic test. This is as genetic testing is by its nature quite contextual and dependent on the disorder and family history. Therefore a session with a genetic counselor is a must both before (pre-test) and after genetic testing results (post-test). Also, there may be a need to test additional family members or to carry out some additional tests. The genetic counselor would also explain the benefits, limitations and scope of the genetic test being recommended. Along with counseling, depending on the type of test along with the clinician certain additional experts such as nutritionists may also be required especially in case of metabolic genetic disorders. The metabolic dietitian provides guideline and protocol-based personalised nutritional guidance in complex metabolic genetic cases or wherever needed.

What are the required testing facilities to get a proper and timely diagnosis?

A common myth about Genetic testing is that there is one test that can give you all the answers. Very often more than one genetic test may be required to get comprehensive answers to decipher a disorder. In addition to various instruments such as Microscopes (Basic to advanced Epifluorescent with Robotics) for Cytogenetic, Sanger Sequencers for Molecular Genetic to Microarrays and Next Generation Sequencers would be required. Equally important is the need to have a team of specialists who can convert the data generated from these systems to actionable information for the clinicians to better help their patients. For example an NGS based test would require technical experts in the lab to prepare, process and sequence the patients sample up to sequencing and data generation. Based on the test being performed then the bioinformatics team would take over to begin the process for deciphering the sequencing data and converting it into an interpretable format. This would be used by the Genome Analyst team to determine how the results should be reported along with Genetic Counselors and Clinical Geneticists who would help correlate the Genetic information with the clinical indications of the patient. Only when all these groups work synchronously would there be effective information that would enable proper diagnosis in a timely manner for each case.

What's the amount of investment that goes into acquiring the testing equipment?

For any organization planning to start genetic testing services; investments need to be made in infrastructure, instruments and skilled manpower.  Depending on the type of genetic testing this can range from a relatively small setup for performing routine karyotyping for blood samples all the way up to high-end molecular biology laboratories wherein cell-free DNA analysis can happen. Important to note is that each type of test has its own laboratory, instrument and manpower requirements. Also, there needs to be an estimate of the number of samples being processed every day. One must also plan for storage and preservation of samples, the data and the reports. 

What makes Lilac Insights lead in the field of reproductive and cancer genetics?

Lilac insights is a leader in the field of diagnostic genetics as there is a balance between delivery of results in the present and a vision for the future. In both reproductive genetics as well as cancer genetics; Lilac Insights offers a comprehensive range of testing services ranging from Cytogenetics to NGS based Testing. These services are offered in our labs based in Navi Mumbai and our newer lab at Bengaluru. Along with the standard diagnostic genetics services, Lilac has also planned expansion to newer aspects of Genetic testing with a keen focus on precision genetic testing, Pharmacogenomics, Consumer/Personalised Genomics and translational genetic research. We are also bringing new world-class technology to India for Non-Invasive Prenatal Screening (NIPS) as well as our recently launched non-invasive Pre-Implantation Genetics Testing for Aneuploidies (ni-PGTA). Along with these services we have a team of highly skilled experts in the field of genetic testing. We also have a growing team of Genetic counselors and Clinical geneticists led by Dr Chaitanya Datar. The goal for Lilac Insights with respect to genetic testing is to provide the clinician and patient with a comprehensive range of testing and counselling services so as to give them better insights into the genetic causes of a disorder and how to better treat/manage the condition and understand the impact on future generations.