Anti-Cancer 'Master Switch' Gene Identified

[Guest guest]

Cold Spring Harbor Laboratory scientists discover new gene that

prevents multiple types of cancer

Cell publishes study titled 'CHD5 is a tumor suppressor at human

1p36'

A decades-old cancer mystery has been solved by researchers at Cold

Spring Harbor Laboratory (CSHL). " We not only found a critical tumor

suppressor gene, but have revealed a master switch for a tumor

suppressive network that means more targeted and effective cancer

therapy in the future, " said CSHL Associate Professor Alea Mills,

Ph.D. The study, headed by Mills, was published in the February

issue of Cell.

Specifically, Mills' discovery identifies CHD5, a protein that

prevents cancer, as a novel tumor suppressor, mapping to a specific

portion of chromosome 1 known as 1p36. When CHD5 is not doing its

job, the machinery within our cells that normally prevents cancer is

switched off. The ability of CHD5 to function as a master switch for

a tumor suppressive network suggests that this gene is responsible

for a large number of diverse forms of human cancers. " CHD5

functions like a circuit breaker that regulates the tumor-preventing

power in our cells—when it blows, cancer occurs, " explains Mills.

Modulation of CHD5 activity may provide novel strategies for better

design of more effective cancer therapies. This gene has remained a

mystery until the discovery by Mills' team.

After they located the region where the tumor suppressor resided,

the Mills team sought to identify which genes in that area were

responsible for tumor suppression. Their results showed that

reducing expression of a single gene--CHD5--made cells that had been

rendered slow growing by adding an extra copy of the region, grow

like normal cells.

The findings of Mills' study will influence the future of cancer

research. It shows that deletion of a part of 1p36 causes cancer and

increased " dosage " of CHD5 triggers extra tumor suppression. One

extra dose, or copy, caused cells to either stop dividing or to

undergo cell suicide by switching on a battery of potent tumor

protective machinery. This work indicates that pharmaceuticals that

switch on CHD5 may provide a way to treat many types of human cancer.

The research team worked with mouse models which enabled them to

investigate the gains and losses of the chromosome segment

corresponding to human 1p36. To extend the research to human cancer,

Mills collaborated with Stanford University researchers Dr. Hannes

Vogel and Dr. Markus Bredel to study whether CHD5 also functioned as

a tumor suppressor in humans. They discovered that glioma, a

specific form of brain tumor, frequently had deletion of CHD5,

demonstrating the important role of CHD5 in human cancer.

This research and discovery was funded largely by private sector

donations which are important to support state-of-the-art research

and discoveries that may not traditionally be funded by the

government. " The advance by Dr. Mills and her team shows that CSHL's

strategy of providing financial resources to outstanding young

scientists pays off towards diagnosing and treating disease and

human suffering, " states CSHL President Bruce Stillman.

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Research results are available online at

http://www.cell.com/content/article/abstract?

uid=PIIS0092867407000530 or in the February 9th issue of Cell.