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Tuesday, October 12, 2010

Molecular block for rare type of cancer

Our genomes include not only genes encoding particular proteins, but also instructions for when to turn on those genes. Those instructions often come in the form of ‘epigenetics’, signals laid over the DNA sequence that do not include changes in the DNA code itself. For example, chromatin (the combination of DNA and protein) may be modified by the addition or removal of proteins that affect whether a gene is expressed.

NUT midline carcinoma (NMC) is a rare but deadly form of cancer affecting children and young adults. The originating tissue is unknown, although it is often found along the vertical centerline of the body. It is identified via a genetic test, since it results from a chromosomal translocation. Two genes that are normally found in completely different regions of the genome become fused, forming a hybrid gene called BRD4-NUT. The resultant protein binds to chromatin, switching on replication and growth cycles, leading to cancer.

James Bradford led a team from Harvard in isolating a compound that blocks BRD4-NUT from binding to chromatin. The chemical was dubbed JQ1, after researcher Jun Qi who was involved in the work.

Animal tests have been promising. Mice with NMC, normally a death sentence, survived if given JQ1. The researchers are in the process of refining and testing JQ1 further and are hopeful that they’ve found an effective therapy for this hitherto incurable type of cancer. Even more importantly, the research may lead to treatments for a wide assortment of cancers that rely on epigenetic control switches.