Transcriptome instability
Transcriptome instability is a genome-wide, pre-mRNA splicing-related characteristic of certain cancers. In general, pre-mRNA splicing is dysregulated in a high proportion of cancerous cells.[1][2][3] For certain types of cancer, like in colorectal and prostate, the number of splicing errors per cancer has been shown to vary greatly between individual cancers, a phenomenon referred to as transcriptome instability.[4][5] Transcriptome instability correlates significantly with reduced expression level of splicing factor genes. Mutation of DNMT3A contributes to development of hematologic malignancies, and DNMT3A-mutated cell lines exhibit transcriptome instability as compared to their isogenic wildtype counterparts.[6]
References
[edit]- â Skotheim, R I; Nees, M (2007). "Alternative splicing in cancer: noise, functional, or systematic?". The International Journal of Biochemistry & Cell Biology. 39 (7â8): 1432â49. doi:10.1016/j.biocel.2007.02.016. PMIDÂ 17416541.
- â Bauer, Joseph Alan; He, Chunjiang; Zhou, Fang; Zuo, Zhixiang; Cheng, Hanhua; Zhou, Rongjia (2009). Bauer, Joseph Alan (ed.). "A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis". PLOS ONE. 4 (3) e4732. Bibcode:2009PLoSO...4.4732H. doi:10.1371/journal.pone.0004732. PMCÂ 2648985. PMIDÂ 19266097.
- â Sveen, A; Kilpinen, S; Ruusulehto, A; Lothe, RA; Skotheim, RI (2015). "Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes". Oncogene. 35 (19): 2413â2427. doi:10.1038/onc.2015.318. PMIDÂ 26300000.
- â Sveen, A; Ã gesen, TH; Nesbakken, A; Rognum, TO; Lothe, RA; Skotheim, RI (2011). "Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival". Genome Medicine. 15 (1): 672. doi:10.1186/1471-2164-15-672. PMCÂ 3219073. PMIDÂ 25109687.
- â Sveen, A; Johannessen, B; Teixeira, MR; Lothe, RA; Skotheim, RI (2014). "Transcriptome instability as a molecular pan-cancer characteristic of carcinomas". BMC Genomics. 3 (5): 32. doi:10.1186/gm248. PMCÂ 4137096. PMIDÂ 21619627.
- â Banaszak, LG; Giudice, V; Zhao, X; Wu, Z; Gao, S; Hosokawa, K; Keyvanfar, K; Townsley, DM; Gutierrez-Rodrigues, F; Ibanez, MdPF; Kajigaya, S; Young, NS (2018). "Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing". Blood Cells, Molecules and Diseases. 69: 10â22. doi:10.1016/j.bcmd.2017.12.002. PMCÂ 6728079. PMIDÂ 29324392.
