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Table 1 Summary of functions of eccDNAs related to cancer

From: Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

Type of cancer Genes Drugs/Treatment Biogenesis Function References
Pancancer (17 different cancer types) EGFR Erlotinib Rearrangement Contributes to intratumoral heterogeneity via the reintegration of EGFRvIII-containing eccDNA elements and by promoting the transcription of EGFR; additional rearrangements and heterogeneity after erlotinib withdrawal. [65]
Pancancer (17 different cancer types) MYC NA Rearrangement Contributes to intratumoral heterogeneity by promoting the transcription of MYC. [65]
Pancancer (prostate cancer, colon cancer, glioblastoma) EGFR, MYC, CDK4 and MDM2 NA NA Promotes the expression of oncogenes (EGFR, MYC, CDK4, and MDM2) encoded on eccDNA by influencing the chromatin organization. [7]
Glioblastoma EGFR Irradiation NA Cells with amplified EGFR on eccDNA exhibit stronger invasive properties and radiation resistance. [72]
Glioblastoma MET Capmatinib NA Amplified MET on eccDNA drives early tumor formation, and the elimination of eccDNA increases the survival benefit. [8]
Glioblastoma MYC NA NA EccDNA harboring MYC amplification contributes to recurrent tumors. [8]
Glioblastoma EGFR Dacomitinib NA EccDNA harboring EGFRvIII mutation amplification drives recurrent tumors upon treatment with dacomitinib. [8]
Glioblastoma EGFRvIII Temozolomide with adjuvant radiation NA EccDNA containing EGFRvIII provides cells with growth advantages. [73]
Glioblastoma MDM2 Erlotinib NA The amplification of MDM2 on eccDNA promotes erlotinib resistance. [70]
Neuroblastoma MYCN NA Involves neo-topologically associated domains The hijacking of enhancers and insulators drives the expression of MYC on eccDNA. [40]
Neuroblastoma MYCN NA DNA repair or replication-associated mechanisms Drives oncogenic genome remodeling and the expression of oncogenes. [6]
Neuroblastoma MYCN Hydroxyurea NA The elimination of amplified MYCN on eccDNAs increases the sensitivity to hydroxyurea. [74]
Cervical cancer DHFR Methotrexate Chromothripsis, BFB Adaptation to increased selection pressure is induced by methotrexate by increasing the DHFR gene copies in eccDNA, which promotes DHFR expression. [43]
Cervical cancer DHFR Methotrexate BFB The amplification of DHFR located on eccDNA promotes resistance to methotrexate. [75]
Breast Cancer DHFR Methotrexate NA Irradiation induces methotrexate resistance due to eccDNA with amplified DHFR. [76]
Oral squamous cell carcinoma MDR1 Hydroxyurea NA Loss of MDR1-carrying eccDNA induced by hydroxyurea increases drug sensitivity. [77]
Colon cancer DHFR Methotrexate NA The elimination of DHFR-containing eccDNA promotes sensitivity to methotrexate and inhibits proliferation. [78, 79]
Colorectal cancer Not define NA Chromothripsis, a process of multistep evolution that drives eccDNA formation eccDNA may drive cancer progression. [80]
Leukemia MYC Hydroxyurea NA Hydroxyurea inhibits tumorigenicity by eliminating amplified MYC on eccDNAs. [81]
Leukemia c-Myc Hydroxyurea and retinoic acid NA Hydroxyurea inhibits tumorigenicity by eliminating c-Myc-bearing eccDNAs. [82]
Undefined microRNA NA NA Expresses functional small regulatory RNA. [64]
  1. NA Not available