Gene testing in young patients may uncover 'cancer families'

More than half of patients with sarcoma, a rare cancer, have mutations that are known to increase the risk of other types of cancer.

The study helps to explain why some families are affected by many different types of cancer, and it may also lead to potential treatments for sarcoma itself.

'This study gives us the most detailed picture yet of the genetics of sarcoma patients, and reveals that in a significant proportion there may be a genetic cause for this rare cancer. The research helps explain why some patients with sarcoma are prone to develop other cancers in their lifetime, and provides new clues to the phenomenon of "cancer families",' said the UK project leader, Professor Winette van der Graaf of the Institute of Cancer Research in London.

The research was led by the Garvan Institute of Medical Research in Sydney, Australia, who selected 1162 patients with sarcoma – a rare cancer that develops in the bones, muscles or soft tissue of the body. They looked for gene variations, such as mutations and deletions, in the DNA of each patient, and they compared these with 6545 matched controls.

They analysed 72 genes in particular that are each associated with an increased cancer risk, and found that 55 percent of the sarcoma patients had at least one variation in known cancer genes – including BRCA2, ERCC2, ATM and ATR. These genes are strongly associated with breast, ovarian, bowel and other cancers, but this is the first time they've been linked to sarcoma. Just over 20 percent of sarcoma patients had two or more variations in the cancer genes analysed.

Sarcoma is known to be strongly associated with the TP53 gene – half of patients with a mutation in this gene developed the cancer before the age of 32. But having two mutations in genes weakly associated with sarcoma was even more deadly – half of these patients had developed cancer by the age of 25.

'This collaborative work also suggests that much of inherited cancer predisposition may be due to defects in multiple genes working together, any one of which would be unlikely to cause cancer on its own. It's an important step forward in our understanding of sarcoma genetics,' said Professor van der Graaf.

Researchers hope this study could lead to earlier detection of sarcoma in high-risk patients and their relatives, allowing for a greater chance of treatment and survival. The families of patients with mutations in cancer genes could also be offered screening and advice.

The researchers say that the work may help in the development of tailored drug treatments for sarcoma patients. Around 19 percent of sarcoma patients had mutations that could be targeted by new or existing cancer drugs.

'Sarcomas are rare types of cancer that disproportionately affect the young, have low survival rates and in which there are currently few treatment options available,' said study co-author Professor Ian Judson of the Institute of Cancer Research. 'If we understand the mechanism by which the cancer arises, we are going to be much better placed to find the right treatment.'

The research was published in The Lancet Oncology.