Oncology



Cancer leaves a common fingerprint on DNA

 

Regardless of their stage or type, cancers appear to share a tell-tale signature of widespread changes to the so-called epigenome, according to a team of researchers. In a study published online in Genome Medicine on 26 August 2014, the investigators say they have found widespread and distinctive changes in a broad variety of cancers to chemical marks known as methyl groups attached to DNA, which help govern whether genes are turned “on” or “off”, and ultimately how the cell behaves. Such reversible chemical marks on DNA are known as epigenetic, and together they make up the epigenome.

“Regardless of the type of solid tumour, the pattern of methylation is much different on the genomes of cancerous cells than in healthy cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine, molecular biology and genetics, oncology, and biostatistics at the Johns Hopkins University School of Medicine. Feinberg led the new study along with Rafael Irizarry, Ph.D., a professor of biostatics at Harvard University and the Dana-Farber Cancer Institute. “These changes happen very early in tumour formation, and we think they enable tumour cells to adapt to changes in their environment and thrive by quickly turning their genes on or off,” Feinberg says.

Feinberg, along with Johns Hopkins University School of Medicine oncology professor Bert Vogelstein, M.D., first identified abnormal methylation in some cancers in 1983. Since then, Feinberg’s and other research groups have found other cancer-associated changes in epigenetic marks. But only recently, says Feinberg, did researchers gain the tools needed to find out just how widespread these changes are.

For their study, the research team took DNA samples from breast, colon, lung, thyroid and pancreas tumours, and from healthy tissue, and analysed methylation patterns on the DNA. “All of the tumours had big blocks of DNA where the methylation was randomized in cancer, leading to loss of methylation over big chunks and gain of methylation in smaller regions,” says Winston Timp, Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. “The changes arise early in cancer development, suggesting that they could conspire with genetic mutations to aid cancer development,” he says.

The overall effect, Feinberg says, appears to be that cancers can easily turn genes “on” or “off” as needed. For example, they often switch off genes that cause dangerous cells to self-destruct while switching on genes that are normally only used very early in development and that enable cancers to spread and invade healthy tissue. “They have a toolbox that their healthy neighbours lack, and that gives them a competitive advantage,” Feinberg says.

“These insights into the cancer epigenome could provide a foundation for development of early screening or preventive treatment for cancer,” Timp says, suggesting that the distinctive methylation “fingerprint” could potentially be used to tell early-stage cancers apart from other, harmless growths. Even better, he says, would be to find a way to prevent the transition to a cancerous fingerprint from happening at all.

Other authors on the paper are Hector Corrada Bravo of the University of Maryland, College Park, and Oliver G. McDonald, Michael Goggins, Chris Umbricht and Martha Zeiger, all of The Johns Hopkins University.
 



Ground-breaking lung cancer breath test in clinical trial


Ground-breaking lung cancer breath test in clinical trial A clinical trial led by University of Leicester respiratory experts into a potentially ground-breaking ‘breath test’ to detect lung cancer is set to get underway at the Glenfield Hospital in Leicester.

It is hoped that the LuCID (Lung Cancer Indicator Detection) programme will lead to a non-invasive method of diagnosing lung cancer in the early stages. The company behind the device, Cambridgebased Owlstone Nanotech, carried out a health economic analysis and determined that detection of early-stage lung cancer could be increased from the current 14.5% to 25% by 2020, it is estimated this could save 10,000 lives and £250 million (about US$384m) of NHS money.

The device works by measuring volatile organic compounds (VOCs) at low concentrations in a patient’s breath and offers a cheaper and smaller alternative to existing detection technologies. Supported by the University of Leicester’s enterprise and business development team and Leicester’s Hospitals, Owlstone was awarded £1m by the NHS Small Business Research Initiative (SBRI) towards the second phase of the LuCID project – the clinical trials.

The aim is to further evaluate Owlstone’s GC-FAIMS (Gas Chromatography – Field Asymmetric Ion Mobility Spectrometry) sensor in a rapid access lung cancer clinic at Glenfield Hospital, Leicester starting later this year. If successful, the project will pave the way to evaluate the technology in GPs’ surgeries and other hospitals.

Billy Boyle, co-founder of Owlstone, said: “If you could change only one thing in the fight against cancer, it would be to detect the disease earlier where existing treatments are already proven to save lives. FAIMS technology has the potential to bring a quick and easy-to-use breath test to a GP’s office.”

The clinical study is being led by Dr Salman Siddiqui, a clinical senior lecturer and adult chest physician at the University of Leicester and Glenfield Hospital with results of the trial expected in early 2016. The study will be delivered by a number of key members of the lung cancer clinical team including Dr Jonathan Bennett, senior lung cancer clinician.

Dr Siddiqui added: “Lung cancer has one of the lowest 5-year survival rates of all cancers, however early diagnosis can greatly improve a patient’s prognosis. Current diagnostic procedures such as a chest X-ray, CT scan and bronchoscopy are costly and not without risks so the benefits of a non-invasive, cheaper alternative are clear.

“This project will seek to identify and evaluate biomarkers in order to improve the accuracy and reliability of breath diagnostic methods. We will also be aiming to establish FAIMS as a faster, less expensive and more portable alternative to gas chromatography- mass spectrometry (GC-MS) for breath diagnosis applications.”

 Date of upload: 20th March 2015

 

                                  
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