染色体非整倍性,也就是说,数字染色体畸变,是癌症的分子标志之一。然而,当用基于测序和阵列的方法研究肿瘤时,染色体数量和倍性状态通常是从大量DNA数据推断的。此外,已发表的与瘤形成相关的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,这可能是由数字染色体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量,并表明良性和恶性肿瘤在偏离正常方面高度异质,二倍体状态。关注112种特定肿瘤类型的染色体数目,由准确的形态学诊断和器官位置定义,并可获得≥50例病例的数据,我们发现了两个主要的簇:一个以近二倍体肿瘤为主,另一个以具有广泛非整倍体和一个或多个全基因组倍增的肿瘤为主.前一组包括大多数良性实体瘤,髓样肿瘤,和恶性基因融合相关的实体瘤,而后者以恶性实体瘤和淋巴瘤为主。对于16种恶性肿瘤,染色体数量的分布可以与TCGA倍性水平数据进行比较。细胞遗传学和分子数据相关性很好,但前者表明克隆异质性水平较高。此处显示的结果表明某些肿瘤类型的共同致病机制,并为分子分析提供参考。
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.