US researchers unveil womb cancer and acute leukaemia genomes

In collaboration with the Press Association

US researchers have published the intricate details of the genetic makeup of two more forms of cancer - acute myeloid leukaemia (AML) and womb (endometrial) cancer.

The analyses will help design more sophisticated clinical trials of new treatments, and could even affect current clinical practice.

In the first paper, published in the journal Nature, the researchers sequenced the genomes of nearly 400 women with womb cancer, and compared this to the DNA inside the cells of their tumours.

This allowed them to group women with genetically similar forms of the disease.

Previously, this form of cancer was known to exist in two main forms - endometriod and serous - generally treated with radiotherapy or chemotherapy respectively.

The new findings showed that, according to DNA analysis, there are actually three types of endometriod cancers, characterised by different molecular fingerprints.

The research also suggested that some endometriod cancers - termed 'copy-number altered' cancers - were similar to serous cancers, and that this could change how they're treated.

"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," the authors write.

The study also showed that serous womb cancer's fingerprint was similar to that of a type of ovarian cancer, and of an aggressive form of breast cancer called 'basal-like' breast cancer.

The findings suggest that some womb cancers could be treated with drugs typically used for the other cancers, said project co-leader Dr Elaine Mardis, co-director of The Genome Institute at Washington University School of Medicine.

For example, a small proportion of women had tumours containing high levels of a protein called Her2. This suggests they could potentially benefit from drugs, such as trastuzumab, that target this protein.

A previous trial of this drug in womb cancer failed, but the authors speculate that this could be because it didn't recruit enough women with this subtype to see an effect.

"We are entering an era when tumours can be evaluated from a genomics standpoint, not just by looking at cancer cells under a microscope," Dr Mardis said.

"This more comprehensive approach provides a clearer picture of the way particular endometrial cancers will behave and will be important to gynaecological oncologists who treat this disease."

The second paper, published in the New England Journal of Medicine, involved 200 patients newly diagnosed with acute myeloid leukaemia (AML), and pinpointed scores of genetic changes driving the disease.

AML is characterised by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.

The findings show that AML cells generally contain far fewer DNA faults than other cancers.

"We now have a genetic playbook for this type of leukaemia," study co-leader Dr Timothy Ley, associate director for cancer genomics at The Genome Institute at Washington University School of Medicine, said.

"We don't know all the rules yet, but we know all the major players. This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy."

Both groups of researchers were part of The Cancer Genome Atlas (TCGA) Research Network, funded by the US National Institutes of Health, which is looking at unravelling cancer's molecular basis, to improve the way the disease is studied and treated.

The project has previously published detailed analyses of other cancer types, for example ovarian and breast cancers.

Dr Safia Danovi, from Cancer Research UK, said such studies were transforming the way cancer was being studied and treated.

"This work is only the first step - it's given scientists a gold mine of information to work with - so the next challenge is to translate these insights into kinder, more effective treatments for cancer patients," she commented.

"It's particularly interesting to see that cancers that arise in different parts of the body - the breast, the ovaries and the womb - can have remarkably similar genetic profiles.

"We now need to see if this means they can be treated similarly, and that will mean carefully designed clinical trials," she added.

Copyright Press Association 2013

References

  • Getz G. et al  (2013). Integrated genomic characterization of endometrial carcinoma, Nature, 497 (7447) 67-73. DOI:
  • Ley, T.J et al Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia DOI: 10.1056/NEJMoa1301689