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)
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. Genes2019, 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.
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. Genes2019, 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.
Abstract
Triploidy in cancer is associated with poor prognosis but its origins remain unclear. Here, based on frequent X-chromosome doubling in male tumours we attempted to differentiate between a random chromosomal origin and whole-genome origin 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 modal chromosome numbers (ploidy) and combinations of sex chromosomes. Karyotype heterogeneity with a distinct near-triploid fraction was observed in all malignant tumour types, especially high in seminoma. For all tumour types, X-chromosome doubling, dominantly presented by XXY, strongly correlated with the near-triploid state (r≈0.9, p<0.001), negatively correlated with near-diploidy, and did not correlate with near-tetraploidy. The proportion of XX,-Y near-triploid karyotypes was variably increased in somatic tumours. 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. We conclude that doubling of the maternal genome followed by fusion with a paternal genome (similar to digyny) is likely responsible for the observed whole genome triploidy and may be causative for cancer initiation. The Y-chromosome may subsequently be lost due to secondary chromosome instability processes.
Keywords
cancer near-triploidy; male tumours; karyotype meta-analysis; XXY; whole genome rearrangements; digyny
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
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.
