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Revealed: secrets of an 80s cancer gene


As technology advances, researchers are finding there’s still a lot they don’t know about genes discovered almost 30 years ago – with important implications for cancer treatment.

Posted on 27 March, 2015 by Claire Hastings

The late 1970s through to the mid-1980s was an important time for cancer research, heralding the discovery of the first cancer genes. In 1986, Dr Stephen Friend and colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, uncovered a gene on chromosome 13 linked to the childhood cancer retinoblastoma.

DNA Strand

Unlike the relatively few cancer genes that had been discovered previously – where the actions of a gene led directly to tumour growth – the researchers noticed that it was the absence of a functioning gene that seemed to cause cancer. Both the maternal and paternal copies were inactive in retinoblastoma tumour cells.

Since the normal function of this gene appeared to be to stop tumour growth, the retinoblastoma gene – RB1 – was deemed an ‘anti-oncogene’ or tumour suppressor gene, the first ever gene to carry this title.

RB1 became well known through its link with the childhood tumour, with which it shares a name, and later became a feature of school lessons about the causes of cancer. The disease is often diagnosed by parents who notice an odd gleam in the eyes of their children in photographs – retinoblastoma affects the reflex of the pupil, so the glare of the camera flash reflects white like a cat’s eye, instead of the usual red-eye effect.

Inheriting a defective copy of RB1 from one parent strongly predisposes children to developing retinoblastoma in early childhood. A mutation in the second copy of the gene often occurs during foetal development in affected children, and this leads to tumours forming in immature cells of the retina – the light-sensing tissue at the back of the eye. If caught in time the disease is usually cured, albeit with some cost to the child’s vision. If left untreated, cancer can spread throughout the body.

Dr Friend and colleagues went on to show that this gene was also lost in other cancers, and RB1 mutations have now been detected in many common cancers, including those of the breast, lung and prostate.

New function for an old gene

Years of research has pointed to RB1 having a critical role in preventing cell division before cells are ready to divide, and RB1 defects can lead to uncontrolled tumour growth.

Now a new study, led by Dr Paul Huang here at The Institute of Cancer Research in London and Professor Sibylle Mittnachtfrom the UCL Cancer Institute, has found that RB1 has an additional important function – in helping to ‘glue’ severed strands of DNA back together.


Making the most of Dr Paul Huang’s expertise in the latest technologies in molecular systems biology and Professor Mittnacht’s in-depth knowledge of RB1, they found that mutations in RB1 prevent the effective fixing of broken DNA strands. This results in chromosome abnormalities which can lead to the development of tumours and drive cancers to evolve into more aggressive forms.

Dr Huang said: “The retinoblastoma gene was one of the first cancer genes to be discovered and is one of the best known of all, so it’s very exciting to have been able to identify a completely new function for it.”

Defects in DNA repair are common in many cancers, and there are drugs, both in existence and in development, that exploit this weakness. The new research suggests that some of these drugs could be effective against tumours with mutations to the retinoblastoma gene.

Professor Mittnacht, who also ran a lab at the ICR for many years before moving to the UCL Cancer Institute, believes we should use this information to rethink how we should treat cancers with mutations in RB1. She says: “Our research could have real implications for cancer patients, and points to new and more effective ways in which these cancers can be treated.”

Dr Huang adds: “There is now a rationale for testing drugs that target DNA repair against cancers with retinoblastoma gene mutations.”

This new study highlights how much we still have to learn about the basic causes of cancer – even when it comes to one of the best-known cancer genes of all.


childhood cancer
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