Cancer as a disease still remains one of the most complex human illness with high degree of morbidity and mortality across the globe. The involvement of multiple risk factors (genetics, hereditary, environmental etc) further adds a huge challenge in understanding the cancer puzzle even with numerous intensive research on this deadly disease. This year marks over six decades since James Watson and Francis Crick described the structure of DNA and almost 11 years since the complete sequencing of the human genome. Simultaneously, we have also witnessed a significant revolution in DNA sequencing technologies (process of determining the order of nucleotides within a DNA molecule) that has already had a profound impact on our understanding of genetics and genome biology, especially in the field of cancer medicine (detection, management and treatment).
Currently we are in the era of Next Generation Sequencing (NGS) technologies which are capable of reading millions of DNA sequences within few hours with high accuracy and reliability in comparison to previous sequencing techniques such as Sanger which are time consuming, laborious and low throughput. NGS is the catch-all term used to describe a number of different modern sequencing technologies including Illumina (Solexa) sequencing, Roche 454 sequencing, Ion torrent, Proton/PGM sequencing and SOLiD sequencing. The advent of NGS has increased the throughput of DNA sequencing by >500,000-fold and drastically plummeting the sequencing costs. As cancer is a genetic disease driven by various heritable or somatic mutations, one can expect problems in many genes. Hence simultaneous detection of these abnormal genes is currently one of the biggest challenges. Infact, cancer being a multifactorial disease, there is an unmet clinical need to screen more and more genes suspected to be involved in pathogenesis. NGS has made it possible to screen multiple gene abnormalities simultaneously; thereby having a significant impact on cancer detection and therapy. Basically, two types of NGS multiple gene panels have become popular worldwide, i.e – Targeted multigene mutation panels for sporadic tumors and whole gene sequencing for hereditary cancers such as breast, ovary, colon, melanoma etc. In addition to this, there has been substantial increase in the number of NGS based multigene mutation panels across the globe. This comprehensive analysis of multiple genomes has enabled clinicians to selectively look for an almost unlimited number of genetic changes that may contribute to the malignant phenotype, identify new targets for therapy and increase the opportunities for choosing the optimal treatment for each patient. For instance, lung adenocarcinoma can now be divided into subtypes with unique genomic fingerprints associated with different outcomes and different responses to particular therapies. Similarly, colon cancer patients whose tumors harbour KRAS gene mutation will not respond to anti-EGFR therapy. Like wise there are plenty of molecular markers which play a decisive role in guiding the therapy in different cancers – KIT gene mutation in gastro-intestinal tumors, BRAF mutation in melanoma, so on and so forth. This approach not only significantly reduces cost, but also saves time and precious tumor samples. This is one of the biggest reasons why NGS is becoming so popular and it is now maturing to the point where it is being considered by many laboratories for routine use.
Hereditary cancer is another big area wherein NGS panels have gained tremendous attention. The genes we are born with may contribute to our risk of developing certain types of cancers such as breast, ovarian, colorectal, melanoma and prostate cancer. If there is a family history of cancer, hereditary cancer screening panels can help to understand your risk for the disease. For example, BRACA gene testing for breast cancer risk, EPCAM/APC/mismatch repair genes for colon cancer risk, PTEN mutations for tumors of the thyroid, breast and endometrium so on and so forth. However, one should also keep in mind that these hereditary cancer panels help in identifying risk only. The interpretation of positive or negative results should be correlated with other factors such as family history. In no way, these tests give diagnosis of a specific cancer. As the technology evolves, so are the challenges associated therein. NGS generates huge amount of data, hence it requires a huge effort to make the data clinically interpretable as well as applicable. Ultimately, a truly successful bench-to-bedside translation requires a multidisciplinary approach where research scientists, bioinformaticians, pathologists, genetic counselors, and clinicians collaborate on genomic data. Discoveries driven by sequencing are set to revolutionize clinical practice, solve complex disease puzzles; leading to the development of novel diagnostic and prognostic tools in cancer for effective patient management.