Functionally-focused algorithmic analysis of high resolution microarray-CGH genomic landscapes demonstrates comparable genomic copy number aberrations in MSI and MSS sporadic colorectal cancer
| Autor: | Hamad Ali, Makia J. Marafie, Milad S. Bitar, Ashraf Al Madhoun, Fahd Al-Mulla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Microarrays lcsh:Medicine Bioinformatics Suppressor Genes 0302 clinical medicine Basic Cancer Research Medicine and Health Sciences Copy-number variation lcsh:Science Genome Evolution Oligonucleotide Array Sequence Analysis Comparative Genomic Hybridization Multidisciplinary Chromosome Biology Applied Mathematics Simulation and Modeling Genomics Bioassays and Physiological Analysis Oncology 030220 oncology & carcinogenesis Physical Sciences Female Microsatellite Instability DNA microarray Colorectal Neoplasms Functional genomics Algorithms Research Article DNA Copy Number Variations Colon Tumor Suppressor Genes Computational biology Biology Research and Analysis Methods Chromosomes Molecular Evolution 03 medical and health sciences Cancer Genomics Genomic Medicine Gene Types medicine Genetics Humans Multiplex ligation-dependent probe amplification neoplasms Colorectal Cancer Evolutionary Biology lcsh:R Rectum Microsatellite instability Cancer Cancers and Neoplasms Biology and Life Sciences Computational Biology Cell Biology Comparative Genomics medicine.disease digestive system diseases 030104 developmental biology lcsh:Q Mathematics Comparative genomic hybridization Microsatellite Repeats |
| Zdroj: | PLoS ONE, Vol 12, Iss 2, p e0171690 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Array-based comparative genomic hybridization (aCGH) emerged as a powerful technology for studying copy number variations at higher resolution in many cancers including colorectal cancer. However, the lack of standardized systematic protocols including bioinformatic algorithms to obtain and analyze genomic data resulted in significant variation in the reported copy number aberration (CNA) data. Here, we present genomic aCGH data obtained using highly stringent and functionally relevant statistical algorithms from 116 well-defined microsatellites instable (MSI) and microsatellite stable (MSS) colorectal cancers. We utilized aCGH to characterize genomic CNAs in 116 well-defined sets of colorectal cancer (CRC) cases. We further applied the significance testing for aberrant copy number (STAC) and Genomic Identification of Significant Targets in Cancer (GISTIC) algorithms to identify functionally relevant (nonrandom) chromosomal aberrations in the analyzed colorectal cancer samples. Our results produced high resolution genomic landscapes of both, MSI and MSS sporadic CRC. We found that CNAs in MSI and MSS CRCs are heterogeneous in nature but may be divided into 3 distinct genomic patterns. Moreover, we show that although CNAs in MSI and MSS CRCs differ with respect to their size, number and chromosomal distribution, the functional copy number aberrations obtained from MSI and MSS CRCs were in fact comparable but not identical. These unifying CNAs were verified by MLPA tumor-loss gene panel, which spans 15 different chromosomal locations and contains 50 probes for at least 20 tumor suppressor genes. Consistently, deletion/amplification in these frequently cancer altered genes were identical in MSS and MSI CRCs. Our results suggest that MSI and MSS copy number aberrations driving CRC may be functionally comparable. |
| Databáze: | OpenAIRE |
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