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.{{Cite journal|year = 2007|pages = 1432–49|issue = 7–8|volume = 39|journal = The International Journal of Biochemistry & Cell Biology|title = Alternative splicing in cancer: noise, functional, or systematic?|pmid=17416541|author1=Skotheim, R I |author2=Nees, M|doi = 10.1016/j.biocel.2007.02.016}}{{cite journal |last1=Bauer |first1=Joseph Alan |last2=He |first2=Chunjiang |last3=Zhou |first3=Fang |last4=Zuo |first4=Zhixiang |last5=Cheng |first5=Hanhua |last6=Zhou |first6=Rongjia |editor1-last=Bauer |editor1-first=Joseph Alan |title=A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis |journal=PLOS ONE |volume=4 |issue=3 |pages=e4732 |year=2009 |pmid=19266097 |pmc=2648985 |doi=10.1371/journal.pone.0004732|bibcode=2009PLoSO...4.4732H |doi-access=free }}{{cite journal | last1 = Sveen | first1 = A | last2 = Kilpinen | first2 = S | last3 = Ruusulehto | first3 = A | last4 = Lothe | first4 = RA | last5 = Skotheim | first5 = RI | year = 2015 | title = Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes | journal = Oncogene | volume = 35 | issue = 19 | pages = 2413–2427 | doi = 10.1038/onc.2015.318 | pmid = 26300000| doi-access = free }} 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.{{cite journal |last1=Sveen |first1=A |last2=Ågesen |first2=TH |last3=Nesbakken |first3=A |last4=Rognum |first4=TO |last5=Lothe |first5=RA |last6=Skotheim |first6=RI |year=2011 |title=Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival |url=http://www.genomemedicine.com/content/3/5/32 |journal=Genome Medicine |doi=10.1186/1471-2164-15-672 |pmid=25109687 |pmc=3219073 |volume=15 |issue=1 |pages=672 |doi-access=free }}{{cite journal |last1=Sveen |first1=A |last2=Johannessen |first2=B |last3=Teixeira |first3=MR |last4=Lothe |first4=RA |last5=Skotheim |first5=RI |year=2014 |title=Transcriptome instability as a molecular pan-cancer characteristic of carcinomas |url= |journal=BMC Genomics |doi=10.1186/gm248 |pmid=21619627 |pmc=4137096 |volume=3 |issue=5 |pages=32 |doi-access=free }} 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.{{cite journal |last1=Banaszak |first1=LG |last2=Giudice |first2=V |last3=Zhao |first3=X |last4=Wu |first4=Z |last5=Gao |first5=S |last6=Hosokawa |first6=K |last7=Keyvanfar |first7=K |last8=Townsley |first8=DM |last9=Gutierrez-Rodrigues |first9=F |last10=Ibanez |first10=MdPF |last11=Kajigaya |first11=S |last12=Young |first12=NS |year=2018 |title=Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing |journal=Blood Cells, Molecules and Diseases |volume=69 |pages=10–22 |doi=10.1016/j.bcmd.2017.12.002 |pmid=29324392 |pmc=6728079 }}