Clinical OMICS

JAN-FEB 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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36 Clinical OMICs January/February 2019 C irculating tumor DNA (ctDNA) is frequently vastly outnumbered by the amount of non-cancer DNA in the blood, especially in cancers with a low tumor burden, or in certain types of cancer such as gliomas and renal cancers. Improving detection methods is of paramount importance to allow the identification of the early stages of cancer through the process of liquid biopsy. Two recent papers led by the Rosenfeld group at the University of Cambridge report improvements in the detection of cell-free tumor DNA (cftDNA), advancing its potential to revolutionize how cancer is diagnosed and treated. In one paper, the researchers focus on fragment length to improve the specific detection of cftDNA among other cell free DNA (cfDNA). With the other, the researchers target cftDNA in the cerebro- spinal fluid (CSF) of glioma patients. Fragment Size Matters In healthy individuals, white blood cells are the primary source of cfDNA. There are expected size patterns of cfDNA based on multiple factors, such as the DNA's availability for cleavage due to interaction with histones. Under certain conditions, such as patients with cancer, other cell sources may contribute to cfDNA in the form of ctDNA. The first paper from this team of researchers suggests that harness- ing the distinct size distribution of ctDNA fragments could improve their detection. Published in Science Translational Medicine, the paper is titled "Enhanced detection of circulat- ing tumor DNA by fragment size analysis". The authors hypothesized that "differences in frag- ment length of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA." In addition, that ctDNA could be utilized for noninvasive genomics analysis of cancer such as the identification of clinically actionable mutations and somatic copy number alterations (SCNAs). Florent Mouliere, Ph.D., assistant professor in the depart- ment of pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, co-first author on the study, and his colleagues, observed the expected cfDNA size pattern in plasma sam- ples from 65 healthy controls. However, in 344 plasma samples from 200 patients with multiple, different forms of cancer, they noticed varying size distributions. Specif- ically, they found shorter fragments of 20 to 150 bp more frequently in patients with melanoma, breast, ovarian, lung, colorectal, and cholangiocarcinoma cancer types, but not in plasma samples from other cancers. Mouliere told Clinical OMICs that the observation of a rel- ative enrichment for ctDNA following size-selection of short fragments was expected. He adds that "our results con- firmed this enrichment for ctDNA, and specific alterations and mutations with both in vitro and in silico methods." However, Moulier noted that "the results of the second half of the paper were more surprising." He explained Advancements in Detection of Cell-Free Tumor DNA in Plasma and CFS Extending LBx Reach By Julianna LeMieux, Ph.D. Breaking New Ground in Liquid Biopsy PASIEKA/SPL / Science Photo Library /Getty Images

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