London Calling 2023: Small extrachromosomal circular DNAs as biomarkers for potential pan-cancer diagnosis and prognosis

Small extrachromosomal circular DNAs (eccDNAs) may be used as cancer biomarkers. However, whether the small eccDNA profile in plasma of cancer patients is representative of that in cancer tissues remains to be elucidated. A nanopore sequencing-based method was performed to sequence small eccDNAs from cancer or normal tissues and paired plasma. Compared with those in normal tissues, small eccDNAs detected in cancer tissues were significantly larger in number and size, along with more even distribution and more diverse formation mechanisms. The small eccDNAs from cancer tissues had different general characteristics and genomic annotation with paired plasma, which may be carcinogenesis. The proportion of small eccDNAs containing some specific genes had great pan-cancer diagnostic value, especially the combination of PLD1 and ATF6 or the combination of ETV6 and ALK. As independent and stable circular DNA molecules, small eccDNAs may be used as ideal biomarkers for pan-cancer diagnosis and prognosis.