Case of woman who survived 12 tumours paves way for early cancer diagnosis

Researchers say the exceptional case of a woman who has survived 12 tumours opens up new avenues for early diagnosis and immunotherapy in cancer.

Scientists discovered that the 12 tumours, five of them malignant (cancerous), are due to the fact that the patient inherited mutations in a gene essential for life from both parents.

According to the researchers, the patient’s immune system naturally generates a strong anti-inflammatory response that fights the tumours.

Understanding how it does this could help stimulate the immune system in other cases, they suggest.

The study also shows how a new technique called single-cell analysis can detect tumours at very early stages, or a predisposition to developing them.

The woman featured in the study first developed a tumour when almost still a baby, followed by others every few years.

In less than 40 years of life, the patient has developed twelve tumours, at least five of them malignant.

Each has been of a different type and in a different part of the body.

The person also has skin spots, microcephaly – a condition where a baby’s head is much smaller than expected – and other alterations.

Marcos Malumbres, head of the Cell Division and Cancer Group at the Spanish National Cancer Research Centre (CNIO), said: “We still don’t understand how this individual could have developed during the embryonic stage, nor could have overcome all these pathologies.”

He added that the study of this unique case opens up a way to detect cells with tumours potentially well in advance of clinical tests and diagnostic imaging.

“It also provides a novel way to stimulate the immune response to a cancerous process,” said Professor Malumbres.

When the patient first visited the CNIO’s Familial Cancer Clinical Unit, a blood sample was taken to sequence the genes most frequently involved in hereditary cancer, but no alteration was detected in them.

Researchers then analysed the female’s entire genome and found mutations in a gene called MAD1L1.

This gene is essential in the process of cell division and proliferation.

Researchers analysed the effect of the mutations, and concluded they cause alterations in the number of chromosomes in the cells – all cells in the human body have 23 pairs of chromosomes.

Animal models have suggested that when there are mutations in both copies of this gene – each coming from one parent – the embryo dies.

To the astonishment of the researchers, the person in this case has mutations in both copies but has survived, living as normal a life as can be expected of someone suffering from ill health.

According to Miguel Urioste, the co-author of the study who headed the CNIO’s Familial Cancer Clinical Unit until his retirement in January this year said no other case like this has ever been described.

He said: “Academically we cannot speak of a new syndrome because it is the description of a single case, but biologically it is.”

While other genes whose mutations alter the number of chromosomes in cells are known, researchers say this case is different because of the aggressiveness, the percentage of aberrations it produces and the extreme susceptibility to a large number of different tumours.

The search team was intrigued by the fact that the five aggressive cancers developed by the patient disappeared relatively easily.

Their hypothesis is that “the constant production of altered cells has generated a chronic defensive response in the patient against these cells, and that helps the tumours to disappear”.

“We think that boosting the immune response of other patients would help them to halt the tumoural development,” explained Dr Malumbres.

Researchers say one of the most important aspects of the study is the discovery that the immune system is capable of unleashing a defensive response against cells with the wrong number of chromosomes.

The findings may open up new therapeutic options in the future, they suggest.

The study is published in the Science Advances journal.