Evidence of gene amplification in the form of double minute chromosomes is frequently observed in lung cancer

Nielsen, James L.; Walsh, Julianna T.; Degen, D; Drabek, Sonya M.; McGill, J.; Hoff, Daniel D. Von

doi:10.1016/0165-4608(93)90219-c

Cited by 36 publications

(15 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On short aberrations, noise may cause segmentation errors, making the exact copy number hard to determine. This is of particular importance for genomic aberrations such as double minutes (DMs), as their numbers vary greatly between cells and the observed copy number reflects an average [14]. To this end, TAPS copy number analysis outputs an additional set of short-segment scatter plots, where the segments produced by circular binary segmentation (CBS) have been further segmented into regions of 200 to 400 markers.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity

et al. 2011

View full text Add to dashboard Cite

We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Some copy number alterations are variable in nature, their genomic content prone to repeated duplication or deletion in future cell generations [14]. In addition, copy number aberrations in tumor cells may arise several times throughout tumor development, and may give rise to different subclones.…”

Section: Introductionmentioning

confidence: 99%

Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The biology of extrachromosomal circular DNA molecules is of particular interest because of their preponderance in tumorigenic cells in vivo (Wahl 1989;VanDevanter et al 1990;Benner et al 1991;McGill et al 1993;Nielsen et al 1993). Extrachromosomal circular DNA frequently harbors amplified oncogenes and drug resistance genes that can provide cancer cells with a selective growth advantage and are formed as a result of gene amplification mechanisms operative in tumor cells (Stark and Wahl 1984;Schimke 1988;Tlsty et al 1989;Livingstone et al 1992;Yin et al 1992;Abken 1995).…”

Section: Introductionmentioning

confidence: 98%

The degradation profile of extrachromosomal circular DNA during cisplatin-induced apoptosis is consistent with preferential cleavage at matrix attachment regions

1999

View full text Add to dashboard Cite

Extrachromosomal circular DNA molecules are prevalent in cancer cells and harbor amplified genes, such as oncogenes and drug resistance genes, that can provide a selective growth advantage to cancer cells. These circular DNA structures include double minute chromosomes (dmin), which can be detected with light microscopy following Giemsa staining, and submicroscopic circular DNA structures referred to as episomes. In this study, we investigated the fate of dmin and episomes in multidrug-resistant human epidermoid KB-VI cells undergoing cisplatin-induced apoptosis-a mode of cell death initially characterized by the fragmentation of chromosomal DNA, while the nuclear membrane remains intact. The circular DNA structures carry amplified copies of the multidrug resistance gene (MDR1). During cisplatin-induced apoptotic cell death, episomes and dmin, as well as native chromosomes, were degraded into high molecular weight DNA fragments of approximately 50 kb in length. DNA fragments in this size range appear to result from the preferential cleavage of matrix-associated regions in chromatin with the subsequent release of 20-30 nm loop domains of chromatin from the nuclear scaffold. Scanning electron microscopy studies were performed and confirmed the presence of 30 nm filaments in a higher-order DNA packing of MDR1-containing dmin and episomes. These combined data provide strong evidence that the higher-order DNA packing of episomes, as well as dmin, is similar to that of native chromosomes and underscore the potential for extrachromosomal DNA amplicons to study the structural and functional organization of chromatin. We discuss the implications of extra-chromosomal DNA matrix associated regions competing with native chromosomal DNA for binding to the nuclear matrix in tumor cells.

show abstract

“…Genomic instability is a commonly observed feature of tumours (Nowell, 1982(Nowell, , 1991Bringuier et al, 1993;Nielsen et al, 1993). Factors intrinsic to tumour cells (such as mutated forms of p53) may predispose these cells to further genomic instability (Weinert and Lydall, 1993).…”

Section: Disaussionmentioning

confidence: 99%

Hprt mutants in a transplantable murine tumour arise more frequently in vivo than in vitro

Wilkinson

Sandhu²,

Breneman³

et al. 1995

Br J Cancer

View full text Add to dashboard Cite

Sumnuary A model system was developed to allow investigation of the frequency at which clastogenic and or mutagenic events occur in situ in a transplantable murine fibrosarcoma tumour (MCIA-Cl) compared with in vitro culture. The marker selected for detecting these events was the X-linked hprt (hypoxanthine-guanine phosphonrbosyltransferase) gene. We found that the hprt gene in MCIA-Cl was not suitable for this purpose, most likely because multiple active copies were present. To circumvent the problem, HPRT -[6-thioguanine (6-TG)-resistant] clones were isolated by inactivating all hprt genes with methylnitrosourea. Spontaneous revertants to hypoxanthine/aminopterin/thymidine resistance (HATR) were isolated and found to be approximately 1000 times more sensitive than the parental tumour to induction of 6-TGR mutants by cobalt-60 y-rays. This sensitivity is expected for a heterozygous marker; these revertants may therefore possess only one functional hprt locus but two or more active X chromosomes. A clone with a stable hprt gene was identified and a neo gene was introduced. The resulting cell line (MN-i 1) could be grown as a subcutaneous tumour in syngeneic C57BL/6 animals. The frequency of mutations arising in vivo in the marker hprt gene could be estimated by cultunrng explanted tumour cells in the presence of 6-TG, using G418 selection to distinguish tumour from host cells. The frequency of mutants in MN-lI cells grown as tumours was found to be 3.4-fold higher than in tissue culture for an equivalent period of time. These data provide the first direct evidence for the existence of mutagenic factors in a tumour environment that might contribute to tumour progression.

show abstract

Evidence of gene amplification in the form of double minute chromosomes is frequently observed in lung cancer

Cited by 36 publications

References 17 publications

Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity

Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity

The degradation profile of extrachromosomal circular DNA during cisplatin-induced apoptosis is consistent with preferential cleavage at matrix attachment regions

Hprt mutants in a transplantable murine tumour arise more frequently in vivo than in vitro

Contact Info

Product

Resources

About