Browsing by Author "Vainshelbaum, Ninel M."

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Meta-analysis of cancer triploidy : Rearrangements of genome complements in male human tumors are characterized by XXY karyotypes
    (2019-08-13) Vainshelbaum, Ninel M.; Zayakin, Pawel; Kleina, Regīna; Giuliani, Alessandro; Ērenpreisa, Jekaterina; Department of Pathology
    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.
  • No Thumbnail Available
    Item
    The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction
    (2022-12) Vainshelbaum, Ninel M.; Giuliani, Alessandro; Salmina, Kristine; Pjanova, Dace; Ērenpreisa, Jekaterina
    The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein–protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer–testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma–germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.
  • No Thumbnail Available
    Item
    When Three Isn't a Crowd : A Digyny Concept for Treatment-Resistant, Near-Triploid Human Cancers
    (2019-07) Salmina, Kristine; Gerashchenko, Bogdan, I; Hausmann, Michael; Vainshelbaum, Ninel M.; Zayakin, Pawel; Erenpreiss, Juris; Freivalds, Talivaldis; Cragg, Mark S.; Erenpreisa, Jekaterina; Rīga Stradiņš University