Preprint Article Version 2 This version is not peer-reviewed

Meta-Analysis of Cancer Triploidy: Whole-Genome Rearrangements in Male Human Tumours Are Characterised by XXY Karyotypes

Version 1 : Received: 5 April 2019 / Approved: 8 April 2019 / Online: 8 April 2019 (10:56:41 CEST)
Version 2 : Received: 13 July 2019 / Approved: 14 July 2019 / Online: 14 July 2019 (09:25:18 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Genes 2019, 10, 613
DOI: 10.3390/genes10080613

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 5 benign tumour 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 tumour types, being especially high in seminoma. For all tumour 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 3 of 5 benign tumour types, especially notable in colon adenoma. Principal Component Analysis revealed a non-random correlation structure shaping the X-chromosome disomy distribution across all tumour 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 secondary from chromosome instability.

Subject Areas

cancer near-triploidy; male tumours; karyotype meta-analysis; XXY; whole genome rearrangements; digyny

Comments (1)

Comment 1
Received: 14 July 2019
Commenter: Jekaterina Erenpreisa
Commenter's Conflict of Interests: Author
Comment: We have improved the article, adding the PCA analysis results as a new paragraph 3.5. Principal Component Analysis (PCA), Table 3, and Fig. 6, and one more author A. Giuliani who performed it. We have resettled the Figures 2 and 3 and added the Fig.7 which is also a Graphical Abstract now. We have also edited the Abstract and text. The main message of the article, the original material, and Conclusions remained the same.
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