Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 h Peripheral lymphocyte culturing and GTG-banding. Reactome database from Cytoscape software version 3.7.1 was used to perform in-silico analysis (functional interaction and gene enrichment). Frequency of chromosomal aberrations (structural and numerical) was found to be significantly higher in patients as compared to controls. The genes harbored by chromosomal regions showing increased aberration frequency in patients were further analyzed in-silico. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. The current study employs the information inferred from chromosomal instability analysis in a non-target tissue for determining the genes and the pathways associated with breast cancer. These results can be further extrapolated by performing either mutation analysis in the genes/pathways deduced or expression analysis which can pinpoint the relevant functional impact of chromosomal instability.

中文翻译：

---

基于染色体不稳定的乳腺癌患者的计算机途径分析

肿瘤中发生的复杂基因组变化是染色体不稳定的结果。在肿瘤细胞中，基因组畸变破坏了涉及各种基因的核心信号通路，因此信号通路的描绘可以帮助理解癌症的发病机理。生物信息学工具可以进一步帮助鉴定基因之间的相互作用网络，从而获得受染色体不稳定影响的所有基因的更大生物学背景。在72 h外周血淋巴细胞培养和GTG显像后，对150位经临床证实的乳腺癌患者以及150位年龄和性别相匹配的健康对照者进行了核型分析。使用Cytoscape软件3.7.1版的Reactome数据库进行计算机内分析（功能相互作用和基因富集）。与对照组相比，发现患者的染色体畸变频率（结构和数值）明显更高。在计算机上进一步分析了由染色体区域隐藏的基因，这些基因显示出患者畸变频率增加。对一组未链接在一起的基因的途径分析表明，基因HDAC3，NCOA1，NLRC4，COL1A1，RARA，WWTR1和BRCA1富含RNA聚合酶II转录途径，该途径与募集期间的募集，起始，延伸和解离有关。转录。当前的研究利用从非目标组织中的染色体不稳定性分析推断出的信息来确定与乳腺癌相关的基因和途径。