Extreme chromosomal instability linked to better survival

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

“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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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 editors

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