Double minutes in human tumor cells

Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63-72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5; 17Xqll.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients'

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“…DMs have a wide variation in size even in a specific cell line. In addition, there is also a great variation in the number of DMs per cell (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…These include double minutes (DMs)' and homogeneously staining regions (HSRs) (8,9). Amplified drug resistance genes and amplified oncogenes have been localized to these structures.…”

Section: Introductionmentioning

confidence: 99%

Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells.

Hoff

Forseth²,

Clare³

et al. 1990

J. Clin. Invest.

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“…Amplified chromosomal regions, known as amplicons, are revealed as either homogenously staining regions or as double minutes (Barker, 1982;Alitalo et al, 1983;Lengauer et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth

et al. 2007

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The amplified region of chromosome 19q13.1-13.2 has been associated with several cancers. The well-characterized oncogene AKT2 is located in this amplicon. Two members of the same gene family (SERTAD1 and SERTAD3) are also located within this region. We report herein the genomic structure and potential functions of SERTAD3. SERTAD3 has two transcript variants with short mRNA half-lives, and one of the variants is tightly regulated throughout G1 and S phases of the cell cycle. Overexpression of SERTAD3 induces cell transformation in vitro and tumor formation in mice, whereas inhibition of SERTAD3 by small interfering RNA (siRNA) results in a reduction in cell growth rate. Furthermore, luciferase assays based on E2F-1 binding indicate that SERTAD3 increases the activity of E2F, which is reduced by inhibition of SERTAD3 by siRNA. Together, our data support that SERTAD3 contributes to oncogenesis, at least in part, via an E2F-dependent mechanism.

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“…DM chromosomes and HSRs are recurrent features in malignant human tumors (11). Recent findings indicate that-like their counterparts in drug-resistant cells-both of these cytogenetic abnormalities may represent amplified DNA (12).…”

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confidence: 99%

Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma.

Alitalo¹,

Schwab²,

Lin³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

640

230

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Two human neuroendocrine tumor cell lines derived from a colon carcinoma contain either numerous double minute chromosomes (COLO 320 DM) or a homogeneously staining marker chromosome (COLO 320 HSR). We found amplification and enhanced expression of the cellular encogene c-myc in both COLO 320 DM and HSR cells, and we were able to show that the homogeneously staining regions of the COLO 320 HSR marker chromosome contain amplified c-myc. From previous and present karyotypes, it appears that the homogeneously staining regions re-

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Double minutes in human tumor cells

Cited by 179 publications

References 71 publications

Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells.

Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells.

Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth

Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma.

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