Structural Variants in the SMC1A Gene Associated With Near‐Haploidy in Undifferentiated Pleomorphic Sarcomas

Abstract

ABSTRACTNear‐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.