Genomic landscape of copy number variation and copy neutral loss of heterozygosity events in equine sarcoids reveals increased instability of the sarcoid genome.

Pawlina-Tyszko, Klaudia; Gurgul, Artur; Szmatoła, Tomasz; Ropka-Molik, Katarzyna; Semik-Gurgul, Ewelina; Klukowska-Rötzler, Jolanta; Koch, Christoph; Mählmann, Kathrin; Bugno-Poniewierska, Monika (2017). Genomic landscape of copy number variation and copy neutral loss of heterozygosity events in equine sarcoids reveals increased instability of the sarcoid genome. Biochimie, 140, pp. 122-132. Elsevier Masson SAS 10.1016/j.biochi.2017.07.006

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Although they are the most common neoplasms in equids, sarcoids are not fully characterized at the molecular level. Therefore, the objective of this study was to characterize the landscape of structural rearrangements, such as copy number variation (CNV) and copy neutral loss of heterozygosity (cnLOH), in the genomes of sarcoid tumor cells. This information will not only broaden our understanding of the characteristics of this genome but will also improve the general knowledge of this tumor and the mechanisms involved in its generation. To this end, Equine SNP64K Illumina microarrays were applied along with bioinformatics tools dedicated for signal intensity analysis. The analysis revealed increased instability of the genome of sarcoid cells compared with unaltered skin tissue samples, which was manifested by the prevalence of CNV and cnLOH events. Many of the identified CNVs overlapped with the other research results, but the simultaneously observed variability in the number and sizes of detected aberrations indicated a need for further studies and the development of more reliable bioinformatics algorithms. The functional analysis of genes co-localized with the identified aberrations revealed that these genes are engaged in vital cellular processes. In addition, a number of these genes directly contribute to neoplastic transformation. Furthermore, large numbers of cnLOH events identified in the sarcoids suggested that they may play no less significant roles than CNVs in the carcinogenesis of this tumor. Thus, our results indicate the importance of cnLOH and CNV in equine sarcoid oncogenesis and present a direction of future research.

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