Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics

Abstract

Double minute chromosomes (DMs) are the cytogenetic hallmark of extra-chromosomal genomic amplification. The frequency of DMs in primary cancer and the cytogenetic features of DMs-positive primary cancer cases are largely unknown. To unravel these issues, we retrieved the Mitelman database and analyzed all DMs-positive primary cancerous karyotypes (787 karyotypes). The overall frequency of DMs is 1.4% (787 DMs-positive cases; total 54,398 cases). We found that DMs have the highest frequency in adrenal carcinoma (28.6%, topography) and neuroblastoma (31.7%, morphology). The frequencies of DMs in each tumor were much lower than in previous reports. The frequency of DMs in malignant cancers is significantly higher than in benign cancers, which confirms that DMs are malignant cytogenetic markers. DMs combined cytogenetic abnormalities are identified and sorted into two groups by principal component analysis (PCA), with one group containing −4, −5, −8, −9, −10, −13, −14, −15, −16, −17, −18, −20, −21, and −22, and the other containing −1p, −5q, +7, and +20. The prominent imbalance in DMs-positive cancer cases is chromosome loss. However, DMs-positive cancer cases, deriving from different morphologic cancers, cannot be clearly divided into subgroups. Our large database analysis provides novel knowledge of DMs and their combined cytogenetic abnormalities in primary cancer.

Centromeres License the Mitotic Condensation of Yeast Chromosome Arms

“…Most of these can have adverse effects on the cell or the organism, either because they hijack the cellular machinery, such as viruses, or by producing genetic noise. For example, in many cancers extra-chromosomal double minutes amplify proto-oncogenes, drive tumorigenesis ( Fan et al., 2011 , Von Hoff et al., 1988 , Turner et al., 2017 ), and contribute to drug resistance ( Kuttler and Mai, 2007 ). In budding yeast, the accumulation of DNA circles in the mother cell through asymmetric segregation is a major determinant of replicative aging (reviewed in Denoth-Lippuner et al., 2014a ).…”

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity

“… Human cells have twenty-three pairs of chromosomes but in cancer, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ECDNA), whose frequency and functional significance are not understood 1 – 4 . We performed whole genome sequencing, structural modeling and cytogenetic analyses of 17 different cancer types, including 2572 metaphases, and developed ECdetect to conduct unbiased integrated ECDNA detection and analysis.…”

Reconstruction of clone- and haplotype-specific cancer genome karyotypes from bulk tumor samples

“…When the derived genome is allowed to have circular chromosomes, which have been extensively observed and studied in cancer [8,21,59,18,56], Theorem 1 provides not only a necessary, but also a sufficient condition for a derived genome to exist. For an extended discussion about DIAG decomposition into segment-adjacency edge alternating walks please refer to supplementary material section S2.1.…”