Tuesday, February 9, 2016

Best Post of October 2015: Chromothripsis!

The next in our "Best of the Month" series comes from October 1, 2015:
The next edition of the World Health Organization Classification of Tumors of the Central Nervous System will feature a new, separate ependymoma subtype: RELA fusion-positive ependymoma. RELA fusion refers to the juxtaposition of the RELA gene (the principle effector of NF-кB signaling which controls DNA transcription and cell survival) to the poorly characterized C11orf95gene. Fusion of these two genes is brought about by chromothripsis, a term first coined in 2011 that literally means "chromosome shattering". Chromothripsis occurs when chromosomal segments first fragment into many pieces and then get stitched back together in random order by DNA repair processes. Seen in the setting of some malignancies, chromothripsis in a particular segment of chromosome 11 can result in C11orf95-RELA fusion, which in turn drives oncogenic NF-кB signaling in ependymoma.

Chromothripsis (literally meaning "chromosomal shattering") can drive oncogenesis

Although chromothripsis is a novel model for oncogenesis, it does not necessarily contradict more established models of progressive cancer development as there is no definitive proof that chromothripsis has to occur as a single catastrophic event. Nevertheless, this is a fascinating area of research which will undoubtedly yield more insights into the progression of at least a subset of cancers.

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