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Telomeres a huge advance in understanding some of the deadliest cancers

October 1, 2014

“We have been chipping away at ALT for many years, and now a very large chunk has fallen off into our hands.” Professor Roger Reddel, Director, CMRI

Researchers at Children’s Medical Research Institute (CMRI), Sydney, have discovered a key process controlling the growth of certain cancer cells, which they believe will lead to new treatments for some of the most deadly types of cancer.

To grow and divide in an unlimited way, cancer cells depend on an ability to prevent the shortening of their telomeres – structures at the ends of chromosomes that shorten as a cell ages.

Previously, CMRI researchers were the first to discover a process called ALT, which prevents telomere shortening in about 10% of cancers, including some deadly brain and bone cancers. They have been studying this complex process ever since, in the expectation that understanding it will open the way to developing new, targeted anti-cancer treatments.

ALT is known to be used by about 15% of all cancers, including a number of brain cancers, osteosarcomas (bone cancer), schwannomas (nerve cancer), and cancers arising in the bladder, cervix, endometrium, oesophagus, gallbladder, kidney, liver, and lung.
In a breakthrough discovery, PhD student Dimitri Conomos, and co-researchers in the Telomere Length Regulation research group, have now found that many of the steps in the ALT process are orchestrated by a molecular machine made up of several different proteins, named the NuRD complex.

One of the most exciting aspects of the work has been finding that all of the molecules in the NuRD complex depend on a single protein (ZNF827) to bring them to the telomeres in cancer cells that use ALT, says research group leader Dr Hilda Pickett, co-author on the study.
‘This means that the function of every one of the proteins in the NuRD complex can potentially be disrupted with just one drug,’ she explains.

‘We have known for quite a while that ZNF827 exists, but haven’t known what it actually does. This protein has now become a prime target for the development of new treatments for some of the worst cancers,’ says Dr Pickett.

The research was made possible through grant funding from the National Health and Medical Research Council, Cancer Institute NSW, and Cancer Council NSW, while an Australian Postgraduate Award supported Dimitri’s studies.

The research has been published online in Nature Structural and Molecular Biology and is available at http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.2877.html

Pictured: Dr Hilda Pickett in the CMRI laboratory

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