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Dr Timothy Mercer


Supported by The Estate of the late Shirley Miners

Chief investigators:  Dr Timothy Mercer

Institute:                     Garvan Institute of Medical Research
Project title:                Backwards splicing of cancer genes in blood
Disease focus:           Myelodysplasia (MDP) and chronic lymphocytic
             leukemia (CLL)
Funding:                     $86,58
Funding period:         2014

Sponsored by the Shirley Miners Bequest

Project summary 

A research team led by Dr Timothy Mercer, from the Garvan Institute of Medical Research, is using a new technology to take a closer look at the role of ‘splicing’ in myelodysplasia (MDP) and chronic lymphocytic leukemia (CLL).

Splicing is an important process that occurs in our cells to produce the proteins coded for by genes. Each human gene is made up of smaller parts known as introns and exons. Splicing cuts out the introns and stitches together different combinations of exons. By alternating the combination of exons that are spliced together, a single gene can encode for multiple protein products.

However, when gene splicing goes wrong it can lead to cancer. Sequencing the genomes of tumours in a wide range of cancers, in particular MDS and CLL, has shown that the cellular machinery responsible for gene splicing is often impacted by mutations.

According to Dr Mercer, researchers don’t understand how these mutations affect the splicing machinery and cause cancer.

“Myelodysplasia and chronic lymphocytic leukaemia often harbour mutations to the splicing machinery,” said Dr Mercer.

“In particular, a splicing gene called SF3B1 is the most commonly mutated gene in myelodysplasia and the second most frequently mutated gene in chronic lymphocytic leukemia.

“In preliminary research, we’ve found that splicing can proceed incorrectly backwards, building incomplete genes and tying the RNA into circular knots. Many of the genes that can be spliced backwards are critical for the cell, and involved in blood cancer development.”

Dr Mercer and his team are aiming to find whether mutations to the SF3B1 and the splicing machinery cause the backwards splicing of these genes, resulting in defective proteins that cause MDS and CLL.

If their theory is correct, it could result in an entirely new pathway by which cancer develops and is potentially common to many cancers.