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When Three Isn’t a Crowd: A Digyny Concept for Treatment-Resistant, Near-Triploid Human Cancers
Open AccessArticle

Meta-Analysis of Cancer Triploidy: Rearrangements of Genome Complements in Male Human Tumors Are Characterized by XXY Karyotypes

1
Cancer Research Division, Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
2
Faculty of Biology, The University of Latvia, LV-1586 Riga, Latvia
3
Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia
4
Environment and Health Department, Istituto Superiore di Sanità, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Genes 2019, 10(8), 613; https://doi.org/10.3390/genes10080613
Received: 5 April 2019 / Revised: 8 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue Chromosomal Heterogeneity and Human Diseases)
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Abstract

Triploidy in cancer is associated with poor prognosis, but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole-genome origins of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and five benign tumor cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing their ploidy and combinations of sex chromosomes. A distinct near-triploid fraction was observed in all malignant tumor types, and was especially high in seminoma. For all tumor types, X-chromosome doubling, predominantly observed as XXY, correlated strongly with the near-triploid state (r ≈ 0.9, p < 0.001), negatively correlated with near-diploidy, and did not correlate with near-tetraploidy. A smaller near-triploid component with a doubled X-chromosome was also present in three of the five benign tumor types, especially notable in colon adenoma. Principal component analysis revealed a non-random correlation structure shaping the X-chromosome disomy distribution across all tumor types. We suggest that doubling of the maternal genome followed by pedogamic fusion with a paternal genome (a possible mimic of the fertilization aberration, 69, XXY digyny) associated with meiotic reprogramming may be responsible for the observed rearrangements of genome complements leading to cancer triploidy. The relatively frequent loss of the Y-chromosome results as a secondary factor from chromosome instability. View Full-Text
Keywords: cancer near-triploidy; male tumors; karyotype meta-analysis; XXY; whole-genome rearrangements; digyny cancer near-triploidy; male tumors; karyotype meta-analysis; XXY; whole-genome rearrangements; digyny
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Vainshelbaum, N.M.; Zayakin, P.; Kleina, R.; Giuliani, A.; Erenpreisa, J. Meta-Analysis of Cancer Triploidy: Rearrangements of Genome Complements in Male Human Tumors Are Characterized by XXY Karyotypes. Genes 2019, 10, 613.

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