Biology:Transcriptome instability

From HandWiki

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. doi:10.1371/journal.pone.0004732. PMID 19266097. Bibcode2009PLoSO...4.4732H. 
  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. PMID 25109687. PMC 3219073. http://www.genomemedicine.com/content/3/5/32. 
  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. PMID 21619627. 
  6. Banaszak, LG; Giudice, V; Zhao, X; Wu, Z; Gao, S; Hosokawa, K; Keyvanfar, K; Townsley, DM et al. (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. PMID 29324392.