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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. 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. 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.

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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. /wiki/Doi_(identifier) ↩

  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648985 ↩

  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. https://doi.org/10.1038%2Fonc.2015.318 ↩

  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 (1): 672. doi:10.1186/1471-2164-15-672. PMC 3219073. PMID 25109687. 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. PMC 4137096. PMID 21619627. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137096 ↩

  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728079 ↩