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Cancer treatment should be based on gene 'fingerprints', says study

7 May 2013
Appeared in BioNews 703

Genetic analysis of tumours provides the key to treating them effectively, according to two studies carried out by The Cancer Genome Atlas (TCGA).

The studies, into endometrial cancer and leukemia, could change the way that tumours and characterised and treated, if findings are validated with large-scale clinical trials.

Endometrial (womb) cancer is typically divided into two main categories: endometrioid, which is treated with radiotherapy; and serous, which is treated with chemotherapy. In order to determine which course of treatment should be followed, pathologists divide the cancers into subtypes by looking at tissue samples on slides.

However, the new research, published in Nature, suggests that the tumours should be classified by their 'molecular fingerprints' instead. When researchers analysed the genomes of almost 400 endometrial tumours, they found that there were four different subtypes which differed in mutation rates and changes in copy number of sections of DNA.

For example, around a quarter of the endometrioid cancers studied had similar mutations in the tumour suppressor gene TP53 to serous tumours, suggesting that they could benefit from similar treatments. The researchers hope that this will change clinical practice, stating that: 'clinicians should carefully consider treating copy-number-altered endometrioid patients with chemotherapy rather than adjuvant radiotherapy and formally test such hypotheses in prospective clinical trials'.

These findings need to be validated with further research, but could mean a move towards more personalised treatment for endometrial cancer. The researchers also found links in patterns of mutations with breast, ovarian, and colorectal cancers, which may mean that endometrial tumours could respond to treatments developed for other types of cancer.

'This study highlights the fact that some tumours with the same characterization by pathologists may have very different molecular features. That’s where these findings will be directly implemented in additional research, and also in the context of clinical trials', said Dr Douglas Levine, a co-leader in the study.

TGCA researchers have also been looking into acute myeloid leukaemia (AML), a cancer of the blood and bone marrow, and the most common form of leukaemia in adults. They analysed samples from 200 people with newly diagnosed disease, and found a relatively low number of mutations in this form of cancer - an average of just 13 per patient - but high levels of epigenetic changes, changes to gene expression that are not caused by the underlying DNA structure.

While the interplay of genes and epigenetics is complex in leukaemia, knowing more about these patterns could help doctors predict how severe the disease is likely to be, and so make better choices for treatment.

'We've never had such a complete picture of AML, and this data set will be mined by researchers for years', said co-study leader Dr Richard Wilson, director of Washington University’s Genome Institute. 'These findings have probably identified every pathway in which a modification – and perhaps new drugs – might be beneficial'.

Cancers Share Gene Patterns, Studies Affirm
New York Times |  1 May 2013
Endometrial and acute myeloid leukemia cancer genomes characterized
National Cancer Institute (press release) |  1 May 2013
Genetic links in aggressive cancer
The Australian |  3 May 2013
Genomes provide clues for treating leukemia, endometrial cancers
Los Angeles Times |  1 May 2013
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The New England Journal of Medicine |  1 May 2013
Integrated genomic characterization of endometrial carcinoma
Nature |  1 May 2013
Study Establishes Basis for Genomic Classification of Endometrial Cancers
The Cancer Genome Atlas (press release) |  1 May 2013
TCGA Researchers Identify Potential Drug Targets, Markers for Leukemia Risk
The Cancer Genome Atlas (press release) |  1 May 2013
US researchers unveil womb cancer and acute leukaemia genomes
Cancer Research UK |  1 May 2013
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