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

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'.