Profiling of DNA copy number in sarcomas by array comparative genomic hybridisation and identification of candidate cancer genes
Year: 2006
Type: dissertation
Study design: Observational Study
Abstract: Cancer is a disease resulting from an accumulation of acquired genetic mutations. The consequence is an uncontrolled growth of cells and disruption of normal control mechanisms. Complex chromosomal aberrations such as amplification and deletion of DNA copy number can lead to the activation and deregulation of oncogenes and tumour suppressor genes respectively, leading to uncontrolled cell growth and giving rise to tumours.\nIn sarcomas, rare malignant tumours of mesenchymal origin, aberrations such as amplifications and losses of DNA are frequently seen. In this project, a panel of 13 leiomyosarcomas (LMS) and seven gastrointestinal stromal tumours (GIST) were analysed by array comparative genomic hybridisation (array CGH). This technique makes it possible to map DNA copy number changes and identify chromosomal regions containing “target genes” responsible for tumour development and/or progression.\nThe most frequent aberrations observed in GISTs were losses of the whole or parts of chromosome 22, seen in all tumours with a minimal recurrent region in 22q12.2-q13.31, as well as chromosome 14, 1p36.32-p13.1, 13q12.11-q33.2, 15q13.2-qtel and 9q13-q34.2.\nIn leiomyosarcomas, the most recurrent aberrations were loss of 10q21.13 and 13q14.2-q14.3. The region in chromosome 17p13.1-p11.2 presented high amplification and its analysis revealed nine candidate genes. Four genomic clones within this region were tested in three LMS samples by fluorescence in situ hybridisation (FISH). LMS1, -10 and -25 showed different levels of DNA copy number although LMS10 was expected to have normal copy number in this region.\nOnly two genes previously cited in literature were contained in the clones tested by FISH although other clones within the amplicon could contain the actual “target” genes; those were MAP2K4 often mutated in many tumour types and SPECC1 involved in juvenile myelomonocytic leukaemia. These genes may be useful in studies of the biology of LMS and should be investigated further.
Author: Ana Heslanyeth Barragan Polania
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2465012582