染色体非整倍性，即染色体数值畸变，是癌症的分子标志之一。然而，当使用基于测序和阵列的方法研究肿瘤时，染色体数目和倍性状态通常是从大量 DNA 数据中推断出来的。此外，已发表的肿瘤相关非整倍性的分子估计通常还包括由各种类型的结构重排引起的基因组失衡，这可能是由染色体数值畸变以外的其他机制引起的。因此，我们使用来自 83,862 个肿瘤的单细胞细胞遗传学数据分析了染色体数目，结果表明良性和恶性肿瘤在偏离正常二倍体状态方面具有高度异质性。着眼于 112 种特定肿瘤类型的染色体数目，通过精确的形态学诊断和器官定位来定义，并从中获得 ≥50 个病例的数据，我们发现了两大类：一类以近二倍体肿瘤为主，另一类以广泛的肿瘤为主。非整倍性和一次或多次全基因组加倍。前一类包括大多数良性实体瘤、髓系肿瘤和恶性基因融合相关实体瘤，而后者则以恶性实体瘤和淋巴瘤为主。对于16种恶性肿瘤类型，染色体数目的分布可以与TCGA倍性水平数据进行比较。细胞遗传学和分子数据相关性良好，但前者表明克隆异质性水平较高。这里提出的结果表明某些肿瘤类型具有共同的发病机制，并为分子分析提供参考。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Chromosomal aneuploidy, that is, numerical chromosome aberrations, is one of the molecular hallmarks of cancer. However, when neoplasms are studied with sequencing- and array-based approaches, chromosome numbers and ploidy states are typically inferred from bulk DNA data. Furthermore, published molecular estimates of neoplasia-associated aneuploidy often also include genomic imbalances resulting from various types of structural rearrangement, which likely result from other mechanisms than numerical chromosome aberrations. We thus analyzed chromosome numbers using single-cell cytogenetic data from 83,862 tumors, and show that both benign and malignant tumors are highly heterogeneous with regard to deviations from the normal, diploid state. Focusing on the chromosome numbers in 112 specific tumor types, defined by both exact morphologic diagnosis and organ location and from which data from ≥50 cases were available, we found two major clusters: one predominated by near-diploid neoplasms and one by neoplasms with extensive aneuploidy and one or more whole genome doublings. The former cluster included most benign solid tumors, myeloid neoplasms, and malignant gene fusion-associated solid tumors, whereas the latter was predominated by malignant solid tumors and lymphomas. For 16 malignant tumor types, the distribution of chromosome numbers could be compared to TCGA ploidy level data. Cytogenetic and molecular data correlated well, but the former indicates a higher level of clonal heterogeneity. The results presented here suggest shared pathogenetic mechanisms in certain tumor types and provide a reference for molecular analyses.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.