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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