Unique case of person who survived 12 tumours reveals new insights into body’s immune system

A story of a patient who has lived through a dozen tumours in less than 40 years is adding new insight into the body’s immune response, researchers who studied the exceptional case say.

In a study published in the journal Science Advances in November, researchers from the Spanish National Cancer Research Centre (CNIO) looked at an individual who first developed a tumour around the time the person was still a baby and has since developed more every few years.

At least five of the 12 tumours developed were malignant and each was a different type and found in different parts of the body.

“We still don’t understand how this individual could have developed during the embryonic stage, nor could have overcome all these pathologies,” Marcos Malumbres, head of the Cell Division and Cancer Group at the CNIO, said in a news release.

Malumbres says the study opens up “a way to detect cells with tumour potential well in advance of clinical tests and diagnostic imaging. It also provides a novel way to stimulate the immune response to a cancerous process.”

The researchers say a blood sample was taken from the patient to sequence the genes found most often in hereditary cancer but no alterations were detected.

But it was after researchers looked at the person’s entire genome that they found mutations in a gene called MAD1L1, which is needed for cell division and proliferation.

The researchers found that the mutations cause alterations in the number of chromosomes a cell has, of which humans have 23 pairs.

Animals with mutations in both copies of this gene die in the embryo. But the researchers say despite having this mutation, the patient survived.

“Academically we cannot speak of a new syndrome because it is the description of a single case, but biologically it is,” Miguel Urioste, co-author of the study and former head of the CNIO’s Familial Cancer Clinical Unit, said.

The researchers say the patient’s five most aggressive cancers disappeared relatively easily.

“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,” Malumbres said.

Given 70 per cent of human tumours have cells with an abnormal number of chromosomes, Malumbres says discovering that the immune system can defend against these types of cells is “one of the most important aspects of this study, which may open up new therapeutic options in the future.”

The scientists used single-cell analysis technology to study the patient and related family members, several of whom have MAD1L1 gene mutations but in only one copy.

The process involved analyzing each blood cell in a sample separately.

The researchers say that the sample contained several hundred chromosomally identical lymphocytes, a white blood cell involved in the body’s immune system, which can proliferate too much and spread to form a tumour.

Because this proliferation happens in the earliest stages of cancer, the researchers suggest that this type of analysis could be used to identify tumours much earlier.