TY - JOUR
T1 - Meta-analysis of cancer triploidy
T2 - Rearrangements of genome complements in male human tumors are characterized by XXY karyotypes
AU - Vainshelbaum, Ninel M.
AU - Zayakin, Pawel
AU - Kleina, Regina
AU - Giuliani, Alessandro
AU - Erenpreisa, Jekaterina
N1 - Funding Information:
Funding: This work has been supported by a grant of the European Regional Development Fund (ERDF) project No. 1.1.1.1/18/A/099 and Alfred Raisner memorial scholarship to N.M.V.
Publisher Copyright:
© 2019 by the authors.
PY - 2019/8/13
Y1 - 2019/8/13
N2 - 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.
AB - 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.
KW - Cancer near-triploidy
KW - Digyny
KW - Karyotype meta-analysis
KW - Male tumors
KW - Whole-genome rearrangements
KW - XXY
UR - http://www.scopus.com/inward/record.url?scp=85071372966&partnerID=8YFLogxK
U2 - 10.3390/genes10080613
DO - 10.3390/genes10080613
M3 - Article
C2 - 31412657
AN - SCOPUS:85071372966
SN - 2073-4425
VL - 10
JO - Genes
JF - Genes
IS - 8
M1 - 613
ER -