High‐throughput sequencing detects signs of cancer recurrence

Abstract

A next-generation, high-speed DNA decoding technology known as high-throughput sequencing (HTS) can detect the earliest signs of potential disease recurrence in nearly twice the number of leukemia patients compared with flow cytometry, according to a study led by researchers at the Fred Hutchinson Cancer Research Center in Seattle, Washington.1 Flow cytometry is currently the gold standard for detecting minimal residual disease, which is when a small number of cancer cells survive treatment. Until recently, minimal residual disease was undetectable. If disease recurrence can be predicted sooner, hematologists could treat it earlier, which would improve survival, according to co-author Harlan Robins, PhD, a computational biologist at the Fred Hutchinson Cancer Research Center. Dr. Robins and his colleagues compared the effectiveness of HTS versus flow cytometry to detect minimal residual disease in 43 patients with acute T-cell lymphoblastic leukemia. Scientists sequenced patients' T-cell receptor genes before and 29 days after chemotherapy and were able to measure their presence in the blood. As a result, they were able to more accurately predict leukemia recurrence. HTS detected minimal residual disease in nearly double the number of patients compared with flow cytometry. Flow cytometry counts the number of cells in the blood with cancer-specific protein on their surface. Although it is considered the gold standard, it has several limitations: It is difficult to standardize across different laboratories, the antibodies used to tag the cancerous cells are expensive, and the sensitivity of the test is low. Researchers found that HTS was at least 20 times more sensitive than flow cytometry in detecting minimal residual disease. HTS can detect any pre-identified clone, and is performed in a centralized laboratory and therefore it produces reliable and reproducible results. In addition, it is highly automated, cost-effective, and objective compared with flow cytometry, which must rely on the skill of the operator and is more subject to human error, according to the study authors. Dr. Robins and his colleagues discovered how to adapt traditional HTS to sequence only variable regions of the human genetic code. These findings will help scientists better understand immunological responses against cancer, autoimmune disorders, and infectious diseases. Reference