Author Interviews, Cancer Research, Genetic Research / 01.12.2020
Similar Frameshift Mutations Identified in Variety of Tumors
MedicalResearch.com Interview with:
Nina Bhardwaj MD PhD
Director of Immunotherapy
Tisch Cancer Institute
Icahn School of Medicine at Mt Sinai
Ward-Coleman Chair in Cancer Research
Professor of Hematology and Oncology
MedicalResearch.com: What is the background for this study?
Response: Neoantigens are novel antigens expressed by tumors as a result of somatic mutations or frame shift mutations. They can be very immunogenic and consequently they are being incorporated into cancer vaccine platforms. In most cases it is necessary to determine each patient’s individual mutations and customize their vaccine antigens accordingly. We sought to identify shared mutations in cancer antigens which are deficient in DNA repair mechanisms namely microsatellite unstable tumors. These tumors have mutations in genes that normally are responsible for ensuring that DNA is properly replicated. Because these genes encode proteins that ensure proper repair around micro-satellite areas (which contain short repeated sequences of DNA and are present in similar regions from one person’s genome to the next), when they are mutated, these regions may not be repaired. Consequently due to nucleotide deletions and insertions one gets frame shift mutations which result in new protein expression which can be shared across tumors, as has been observed for a few regions. We therefore did a comprehensive study of a subset of tumors to determine the breadth of shared frame shift mutations.
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