Cancer Research Division, Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia.
Faculty of Biology, The University of Latvia, LV-1586 Riga, Latvia.
Genes (Basel). 2019 Aug 13;10(8):613. doi: 10.3390/genes10080613.
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. 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 ( ≈ 0.9, < 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.
癌症中的三倍体与预后不良有关，但其起源仍不清楚。在这里，我们试图区分癌症三倍体的随机染色体起源和全基因组起源。我们对从 Mitelman 数据库中提取的 15 个男性恶性和 5 个良性肿瘤队列（2928 个核型）进行了荟萃分析，比较了它们的倍性和性染色体组合。在所有恶性肿瘤类型中都观察到明显的近三倍体分数，在精原细胞瘤中尤其高。对于所有肿瘤类型，X 染色体加倍，主要表现为 XXY，与近三倍体状态密切相关（≈0.9，<0.001），与近二倍体呈负相关，与近四倍体不相关。在五种良性肿瘤类型中的三种中也存在较小的近三倍体成分，在结肠腺瘤中尤为明显。主成分分析显示，在所有肿瘤类型中，X 染色体单体性的非随机相关结构塑造了 X 染色体单体性的分布。我们认为，母体基因组的加倍随后与父本基因组的pedogamic 融合（可能是受精异常 69，XXY 二倍体的模拟）与减数分裂重编程相关，可能导致观察到的基因组互补的重排，从而导致癌症三倍体。Y 染色体的相对频繁丢失是染色体不稳定性的次要因素。
