Bisognin Andrea, Bortoluzzi Stefania, Danieli Gian Antonio
Department of Biology, University of Padua, 35131, Padova, Italy.
BMC Bioinformatics. 2004 Jun 3;5:68. doi: 10.1186/1471-2105-5-68.
Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy.
A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma.
In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.
横纹肌肉瘤是一种相对常见的软组织肿瘤,可能是由于骨骼肌干细胞生长和分化的调节紊乱所致。鉴定在正常骨骼肌和横纹肌肉瘤中差异表达的基因,可能有助于理解肿瘤发生机制、发现诊断和预后标志物以及识别药物治疗的新靶点。
开发了一个Perl代码网络客户端,以自动获取大量基因的基因组图谱位置。该软件基于通过序列比对在人类基因组浏览器上进行自动搜索,每个基因仅需一个转录序列即可。通过这种方式,我们获得了横纹肌肉瘤或骨骼肌中表达的基因的组织特异性染色体图谱。随后,开发了Perl软件,通过使用滑动窗口来计算沿染色体的基因密度。确定了33个主要在横纹肌肉瘤中表达的基因所在的染色体区域。同样,检测到48个染色体区域,其中包括可能与分化骨骼肌功能相关但在横纹肌肉瘤中沉默的基因。
在本研究中,我们开发了一种方法及相关软件用于组织中基因组表达的比较分析,并且我们鉴定出了在人类骨骼肌和肺泡横纹肌肉瘤中显示差异基因表达的染色体片段,这些片段似乎是含有与肺泡横纹肌肉瘤起源相关基因的候选区域,这些基因可能是药物治疗和/或肿瘤标志物开发的靶点。