Small polydispersed circular DNA contains strains of mobile genetic elements and occurs more frequently in permanent cell lines of malignant tumors than in normal lymphocytes

Abstract

Abstract. Small polydispersed circular DNA (spcDNA) belongs to the extrachromosomal pool of DNA and is composed of heterogeneous DNA circles. Whether spcDNA has a special function is currently unclear but their occurrence was suggested to be linked to genetic instability. In this study we investigated as to whether human lymphocytes from healthy volunteers also harbour spcDNA and whether spcDNA is present in all permanent cell lines from human normal and malignant tissues. Moreover, we were interested to see whether spcDNA contains sequences of mobile genetic elements. Our results show that spcDNA is present in all samples investigated yet the amount is lower in normal lymphocytes when compared to cancer cell lines (5.4 vs. 17.8%). Alu sequences were present in 12/16 cancer cell lines whereas LINE-1 (L1) sequences were present in 15 of them. Six tumor cell lines also contained telomeric sequences. In contrast to that, spcDNA of normal lymphocytes contains Alu and L1 sequences only in 3/16 cases and no telomeric sequences at all. Our findings suggest a direct dependency of the amount of Alu and L1 sequences on that of spcDNA. Beside these repetitive sequences, sequencing of spcDNA revealed in most cases chromosomal sequences of almost all chromosomes without an increased frequency of single regions. We suggest that the whole spcDNA including retrotranspositional elements and telomeric sequences may play a role for chromosomal rearrangements and genomic instability.

Restricting retrotransposons: a review

“…Recombination, replicon misfiring, modified TPRT, and reverse transcription models have been proposed to explain these extrachromosomal DNAs [ 404 – 407 ]. Their copy numbers are elevated in cancer cells and associated with genome instability [ 408 , 409 ]. Still a poorly studied class of mammalian copy number variants, spcDNAs could conceivably be an additional off-target source of amplicons for some PCR-based analyses of genomic retrotransposon insertions.…”

Circular retrotransposition products generated by a LINE retrotransposon

“…As these mechanisms involve retroviral intermediates, they seem unlikely to explain the formation of LINE circles. A less-specific class of circular DNA, small dispersed circular DNA (spcDNA), has been found to be present in essentially all mammalian cells (70,71). spcDNA consists of heterogeneous circles of sizes from hundreds to thousands of base pairs, and spcDNA is increased in cells with genome instability (70,71).…”

“…A less-specific class of circular DNA, small dispersed circular DNA (spcDNA), has been found to be present in essentially all mammalian cells (70,71). spcDNA consists of heterogeneous circles of sizes from hundreds to thousands of base pairs, and spcDNA is increased in cells with genome instability (70,71). spcDNA appears to be derived from chromosomal DNA and contains unique sequence, non-coding sequence and repetitive elements (including Alus and L1s).…”

Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance

“…Therefore, the function of spcDNA in telomere regulation might have potential roles in the surveillance of tumor progression. In addition, spcDNA levels are more than 3-fold higher in cancer cells than in normal cells [62] and are further enhanced by treatment with carcinogen [60]. Other reports have shown that the elevated amount of spcDNA is considerably connected with proliferating melanoma cells [63].…”