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
  1. Skotheim, R I; Nees, M (2007). "Alternative splicing in cancer: noise, functional, or systematic?". The International Journal of Biochemistry & Cell Biology. 39 (7–8): 1432–49. doi:10.1016/j.biocel.2007.02.016. PMID 17416541.
  2. 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. PMC 2648985. PMID 19266097.
  3. 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): 2413–2427. doi:10.1038/onc.2015.318. PMID 26300000.
  4. Sveen, A; Ågesen, 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: 672. doi:10.1186/1471-2164-15-672. PMC 3219073. PMID 25109687.
  5. 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. PMC 4137096. PMID 21619627.
  6. 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: 10–22. doi:10.1016/j.bcmd.2017.12.002. PMC 6728079. PMID 29324392.
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