Splicing and survival – linked in colorectal cancer?

New research by Rolf I. Skotheim and colleagues, recently
published in Genome Medicine, provides evidence for the occurrence of aberrant
splicing events in colorectal cancer. Skotheim and colleagues, from Oslo
University Hospital, describe transcriptome instability as a characteristic of
colorectal tumors that is associated with splicing factor expression and,
interestingly, poor patient survival.

Colorectal cancer is one of the most commonly diagnosed
cancers and affects both men and women. On the molecular level, the disease
results from the accumulation of genetic alterations that are frequently
brought about by inherent genomic instabilities, such as chromosomal instability
and microsatellite instability. In their study, Skotheim and colleagues sought to determine
whether instability at the mRNA level is also a feature of colorectal cancer.

The investigators performed a global analysis of
the transcriptomes of two independent sets of colorectal cancer tissue samples,
using exon microarrays.Their analysis revealed deviating mRNA splice variant patterns
across the tumor samples, indicating that the disruption of alternative
splicing is a widespread event in colorectal cancer. This feature, which the
researchers term transcriptome instability or “TIN” was found to be negatively correlated
with splicing factor expression levels. By
analyzing the associated clinical data, Skotheim and colleagues also demonstrate
that TIN is linked with a lower chance of survival in colorectal cancer

This research highlights
a global characteristic of colorectal cancer that could serve as a key
molecular classifier of tumors and has potential prognostic value, which could,
in the future, improve survival rates for the disease.  

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