Picture a haystack brimming with needles, symbolising a large number of mutations prevalent in cancer. Conventional methods prioritise the larger, more prevalent needles -the common mutations – which are easier to detect. Yet, amid this sea of mutations lie smaller and rarer needles – singleton mutations – which are often overlooked and may hold the key to understanding cancer development.
At the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, researchers, led by Dr Amit Dutt (who is now with the Department of Genetics, University of Delhi), have developed a unique tool to detect these rare mutations.
“These rare mutations, often overlooked, could harbour critical insights into variants of unknown significance (VUS), crucial for understanding the disease,” Dr Dutt told The Indian Express.
Dr Dutt, along with lead author Sanket Desai, Suhail Ahmed, and others, have pioneered a groundbreaking tool known as Dome (Domain Driver Mutation Estimator). “This new tool for detecting rare mutations has the potential to impact the field of oncology by helping doctors understand the nuances of these changes in individual patients,” said Dr Dutt. The study has been published in NAR Cancer, a highly prestigious Oxford Press Journal.
How Dome operates
Dome represents an advanced computer program designed to scrutinize the genetic composition of tumours across a diverse cohort of cancer patients. It goes beyond detecting mutations, instead focusing on their precise locations within genes.
“Genes comprise distinct sections known as domains, each endowed with specific functionalities. Mutations occurring within these domains are more likely to disrupt protein function, potentially contributing to cancer progression,” said Dr Dutt.
Sanket Desai, the lead author of the study explained, “Dome meticulously analyzes the positioning of mutations, particularly those akin to established cancer-causing mutations or those resistant to current therapies. The primary emphasis lies on mutations within conserved protein domains that are important for protein function.”
How this new tech will benefit patients
By pinpointing novel rare mutations implicated in cancer, Dome facilitates the development of therapies tailored to each patient’s unique cancer profile. The ability to analyze variants of unknown significance, based on the gene-specific locations, can help predict cancer progression in the patient. This insight equips clinicians with pertinent information for treatment decision-making. The tool that was recently developed has been able to identify 32,917 novel mutations of significance that are likely to be associated with cancer.
Way forward
“Dome is likely to emerge as a formidable tool poised to integrate seamlessly into the arsenal of every oncologist, aiding in the design of precision medicine tailored to individual patient mutation profiles,” said Dr Dutt.
While Dome presently focuses on a specific subset of mutations within genes, the importance of other mutation types cannot be discounted. Validation of its predictions through further research remains imperative to ascertain their clinical relevance.
“Despite these considerations, Dome represents a monumental stride in the identification of rare cancer mutations. This tool serves as a key to unlocking the enigma shrouded within these mutations, paving the way for more personalized and efficacious cancer therapies in the years to come.” said Suhail Ahmed, the second author of the study.
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