It has been less than a year and a half since the St Jude and Canadian researchers came out simultaneously with publications on histone H3 mutations in pediatric glioblastoma and DIPG. These were the first ever reports on a "recurrent mutation in a regulatory histone in humans to case cancer and it seemed that those mutations may be drivers to alter the chromatinc architecture underlying the formation of pediatric GBMs and DIPGs. The H3 mutation specifically related to DIPGs seems to be K27M.
This seemed to generate a huge amount of interest in pediatric high grade glioma/DIPG research as this SNO/PBTF Pediatric Neuro-Oncology Basic and Translational Research Conference held in Fort Lauderdale this week had several abstracts on this exact subject. In fact 4 of the 11 abstracts in the brainstem glioma section included K27M in their title.
Functional Analysis of the H3.3-K27M Mutaton in DIPG
University of Toronto, Duke University, The Hospital for Sick Children
H3.3 K27M accelerates PDGR-induced brainstem gliomagenesis in vivo
Duke Univeristy and Laboratory of Chromatin Biology and Epigenetic (NY)
Targeting the histone H3.3-K27M mutation for the treatment of diffuse intrinsic pontine gliomas
UCSF and Georgetown
The type of histone H3-variant K27M mutation drives the agressiveness of Diffuse Intrinsic Pontine Gliomas
France and UK
In addition, another abstract lists that all the 20 previsously untreated DIPG specimens in their study had the K27M mutition. This abstract entitled "The genomic landscape of treatment naive DIPG biopsy samples" was a combined effort from Paris, France; Barcelona, Spain; London, UK and Vancouver, Canada.
It would seem that this K27M mutation is going to dominant upcoming discussions regarding DIPG. The Allis-Becher research alliance has already produced an elegant paper coming out electronically ahead of print the end of March in Science. This article found that the K27M point mutation is specific to the for the mistake of methionine for lysine at that location. No other amino acid mistake in production causes the same problems. These authors propose that this mutation inhibits a specific complex which promotes tumor formation. It is more complex than that but that is the general idea.
The potential of importance is varied when looking at these abstacts. This K27M mutation could be:
-"one of the first prognositic markers when judging results of prospective trials"
-"a target for novel intervention"
-and a mechanism for DIPG formation.
For those interested in DIPG research, I predict the K27M and other histone mutation research is going to be in the forefront in the near future.
Reference:
Brainstem Tumors, Radiaiton Therapy and Medulloblastoma (Platform Presentation Abstracts)
https://soc-neuro-onc.conference-services.net/programme.asp?conferenceID=3467&action=prog_list&session=26434
Inhibition of PRC2 Activity by a Gain of Function H3 Mutation Found in Pediatric Glioblastoma
http://www.ncbi.nlm.nih.gov/pubmed/23539183
Exceptional new Allis lab Science paper on exploding area of histone H3.3 in pedaitric brain cancer
http://www.ipscell.com/tag/h3-3-k27m/
