2019 June ; 570(7761): 385–389 | Stephen Cristiano et al.
The study developed an approach to evaluate the fragmentation patterns of cell-free DNA (cfDNA) across the genome, aiming to improve the detection and early diagnosis of cancer. The researchers found that cfDNA profiles in healthy individuals reflected nucleosomal patterns of white blood cells, while cancer patients had altered fragmentation profiles. They applied this method to analyze cfDNA from 236 cancer patients and 245 healthy individuals, achieving sensitivities ranging from 57% to >99% among seven cancer types at 98% specificity, with an overall AUC of 0.94. The fragmentation profiles could identify the tissue of origin of cancers in 75% of cases. Combining cfDNA fragmentation analysis with mutation-based analyses detected 91% of cancer patients. The results highlight important properties of cfDNA and provide a proof-of-principle approach for screening, early detection, and monitoring of human cancer.The study developed an approach to evaluate the fragmentation patterns of cell-free DNA (cfDNA) across the genome, aiming to improve the detection and early diagnosis of cancer. The researchers found that cfDNA profiles in healthy individuals reflected nucleosomal patterns of white blood cells, while cancer patients had altered fragmentation profiles. They applied this method to analyze cfDNA from 236 cancer patients and 245 healthy individuals, achieving sensitivities ranging from 57% to >99% among seven cancer types at 98% specificity, with an overall AUC of 0.94. The fragmentation profiles could identify the tissue of origin of cancers in 75% of cases. Combining cfDNA fragmentation analysis with mutation-based analyses detected 91% of cancer patients. The results highlight important properties of cfDNA and provide a proof-of-principle approach for screening, early detection, and monitoring of human cancer.