Extreme chromosomal instability linked to better survival

Cancer Research UK

Cancer Research UK scientists have revealed that classifying tumours according to their levels of chromosomal instability could improve predictions for patient survival, helping doctors plan treatment strategies. The research is published in Cancer Research, today.

Scientists at Cancer Research UK’s London Research Institute analysed the chromosomal instability (CIN) status of more than 3,000 cancer patients. The findings were linked to patient survival data.

The scientists found that patients whose tumours had moderate CIN were less likely to survive than those with very low levels of CIN. But, intriguingly, tumours with the most extreme chromosomal instability – including some receptor negative breast cancers - had a better outcome.

Chromosomally unstable cells are created when cell division faults can create more - or fewer - than the usual 46 chromosomes in daughter cells. These cells are linked to poor survival of patients because potentially cancer-causing mistakes are replicated haphazardly when cells divide. This generates differences from one cancer cell to the next which may enable the cancer to resist drug treatment.

The results suggest that some chromosomal instability is advantageous to cancer cells - which continue to survive and divide despite the abnormalities. But once chromosomal instability exceeds a certain threshold, the cancer cell cannot function effectively – and may die.

Lead author, Dr Charles Swanton, head of translational research at Cancer Research UK’s London Research Institute, said: “It may sound paradoxical but a key challenge in cancer medicine is to determine which patients won’t derive any additional benefit from cancer chemotherapy.

“This may either be because patients are resistant to certain drugs - or that they have an excellent chance of survival without the need for chemotherapy.

“Identifying distinct patient subgroups might help doctors plan personalised cancer care and avoid unnecessary treatment.”

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “These results suggest there is a tipping point for chromosomal instability and that cancer cells that exceed this threshold are unlikely to persist beyond initial treatment.
“Identifying patients who fall either side of the tipping point could help doctors distinguish high and low risk groups and target them with appropriate treatments.”

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References

Nicolai J. Birkbak et al. Cancer Research. Paradoxical relationship between chromosomal instability and survival outcome in cancer. doi: 10.1158/0008-5472.CAN-10-3667

Notes to Editor

The team analysed the chromosomal instability status (CIN) of 2125 breast cancer tumours from 13 separate studies. Tumours with the most extreme chromosomal instability were mainly cancers that were oestrogen receptor negative. The team found that extreme CIN/ER negative tumours were associated with improved survival compared with tumours which had less extreme chromosomal instability.
They also studied the CIN status of ovarian cancer tumours, non-small cell lung cancer and gastric cancer from 1,032 patients across a further six separate studies. The findings were linked to patient survival data.