Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma

摘要: Osteosarcoma (OS) is an aggressive bone tumor with complex abnormal karyotypes and a highly unstable genome, exhibiting both numerical- structural-chromosomal instability (N- S-CIN). Chromosomal rearrangements genomic imbalances affecting 8q24 are frequent in OS. RECQL4 gene maps to this cytoband encodes putative helicase involved the fidelity of DNA replication repair. This protective function protein relevant because often patients Rothmund-Thomson syndrome have constitutional mutations carry very high risk developing To determine relative level expression OS, 18 sporadic tumors were studied by reverse transcription-polymerase chain reaction. All overexpressed comparison control osteoblasts, fluorescence situ hybridization analysis showed that levels strongly copy number-dependent. Relative N- S-CIN determined classifying number transitions within array comparative profiles enumerating frequency break-apart using region-specific probes. Although there was no evidence disruption OS led elevated RECQL4, marked association between increased overall S-CIN, transition higher RECQL4.