Abstract：
Near-haploidization, that is, loss of one copy of most chromosomes, is a relatively rare phenomenon in most tumors, but is enriched among certain soft tissue sarcomas, including undifferentiated pleomorphic sarcoma (UPS). Presumably, near-haploidization can arise through many mechanisms. This study aimed to identify gene rearrangements that could cause near-haploidization. We here present two UPS in which near-haploidization was an early event, identified through single nucleotide polymorphism (SNP) array analysis. One of the cases was studied further using whole genome and transcriptome sequencing, as well as cytogenetic and molecular cytogenetic methods. Both tumors had chromosomal rearrangements in the form of copy number shifts/structural variants affecting the SMC1A gene. These findings suggest that cohesin defects could contribute to mitotic errors resulting in massive loss of chromosomes. SMC1A encodes one of the components of the cohesin multiprotein complex, which is critical for proper alignment of the sister chromatids during S-phase and separation to opposite spindle poles. Further studies should explore the role of cohesin defects in near-haploidization in other sarcomas and to clarify its role in tumor development.
摘要：
近单倍体化，也就是说,大多数染色体的一个拷贝丢失,在大多数肿瘤中是一种相对罕见的现象，但富含某些软组织肉瘤，包括未分化多形性肉瘤（UPS）。大概,近单倍体化可以通过许多机制产生。本研究旨在鉴定可能导致近单倍体化的基因重排。我们在这里介绍两个UPS，其中近单倍体化是早期事件，通过单核苷酸多态性（SNP）阵列分析鉴定。使用全基因组和转录组测序进一步研究了其中一个案例，以及细胞遗传学和分子细胞遗传学方法。两种肿瘤都具有影响SMC1A基因的拷贝数移位/结构变体形式的染色体重排。这些发现表明，粘附素缺陷可能导致有丝分裂错误，从而导致染色体大量丢失。SMC1A编码cohesin多蛋白复合物的成分之一，这对于在S相期间姐妹染色单体的正确对齐和分离到相反的主轴极至关重要。进一步的研究应探讨粘附素缺陷在其他肉瘤近单倍体化中的作用，并阐明其在肿瘤发展中的作用。
