The unique case of a woman who has survived 12 tumors can help improve cancer diagnosis

Today the story of a unique woman in the world is revealed: a Spanish woman who suffered and overcame 12 tumors, five of them malignant, before turning 40 years old.

Her first cancer was detected when she was two and her last at 28. The doctors and scientists who have treated her cannot explain how she can still be alive.

Her case can help improve early diagnosis and develop new cancer treatments.

Doctor Miguel Urioste remembers the first time he met the patient, a woman who is now 36 years old and whose identity has not been revealed to protect her privacy.

It was in 2015. By then she had already undergone five cancer treatments for tumors in various organs and surgeries to remove other non-cancerous malformations.

No one up to that point had tried to connect the dots and try to explain what was causing such a spectacular cancer rate.

The woman was small in size, had spots on her skin, microcephaly, but intellectually she was perfect, recalls Urioste, head of the Family Cancer Unit at the Cancer Research Center (CNIO) until he retired last January.

“We traced her family tree and everything seemed in order;

parents and sisters had no problems;

it didn't fit with any known clinical picture,” he adds.

The researchers analyzed several genes of the patient in search of common mutations that multiply the risk of suffering from tumors.

None showed defects.

So he began a search with a technology only available in leading molecular biology research laboratories: single-cell sequencing.

This system makes it possible to extract thousands of cells from the blood of the patient and her relatives and read the complete genome of each one of them.

The results of the investigation, published this Wednesday in

, reveal that this unique case is due to a genetic mutation that had never been observed in humans.

This woman had inherited from each of her parents a mutated copy of the

gene .

The few scientific references that existed about mutations in this gene came from studies with mice: if the animal had it, it was never able to be born alive.

“It was very difficult to understand how this woman could survive with this mutation;

There had to be something else that had helped her escape”, explains Marcos Malumbres, head of the Cell Division and Cancer group at the CNIO, who participated in the genetic studies of the patient and her family.

Since a sperm fertilizes an egg and an embryo is formed, each cell carries within it the instructions to grow, multiply, transform into neurons, heart or bone and give rise to a healthy baby.

Those instructions are the genome: a book containing 3,000 million letters of DNA structured in 46 chapters called chromosomes.

This patient's doubly mutated gene caused cell growth to go haywire.

Some cells inherited far more chromosomes than they should, and others far fewer.

The body's own safety mechanisms should have caused a miscarriage, but they didn't.

The key to this woman's survival seems to lie in her own illness.

Up to 40% of her blood cells have too many or too few chromosomes, a type of defect known as genomic instability, which is a hallmark of cancer.

The patient's immune system had reacted to this threat with widespread inflammation.

Her defenses were on continuous red alert.

Her mutation condemned her to suffer from cancer much more frequently, but her immune system was highly stimulated, which favored her better identification and destruction of tumor cells, explains CNIO biochemist Carolina Villarroya, first author of the study.

“His genetic defect of hers has ended up protecting her.

She has been cured very well of all malignant tumors after surgery and treatments;

partly thanks to her immune system”,

Explain.

In addition, this woman's tumors have a very high genomic instability, which is "a weak point" for her survival, adds the scientist.

The patient has not developed tumors since 2014. She lives alone, has a job and leads a normal life despite having to be closely monitored by doctors.

“I spoke with her a few days ago and she is fantastic”, sums up Urioste.

For now, the team has resisted naming a new disease for this patient, because only one case is known.

They have preferred to include it in a group of rare genetic disorders known as "variegated mosaic aneuploidies".

Until now, three genes responsible for this disorder were known.

People who suffer from it have a higher risk of cancer and may develop one or two tumors throughout their lives.

Undoubtedly, this fourth cause, the mutation in

is the one that generates the most cancer, says Urioste.

"This is also the patient who has survived this kind of ailment the longest, because most of them usually die in childhood," she points out.

Those responsible for the study believe that the extraordinary case of this patient will help improve cancer diagnosis and develop new treatments.

One of the most outstanding results is that researchers have managed to detect small colonies of cells that have chromosomal defects characteristic of leukemia.

It may be a pre-cancer.

Or not.

This is the potential of single cell sequencing, Malumbres highlights.

"I think this technology should be in hospitals 10 years from now," she says.

But she adds that she would not like to be in the shoes of doctors who detect this type of genetic defect in a patient and cannot apply any treatment, because there is still no cancer.

For Urioste, it is obvious what these doctors should do: monitor the patient more closely to detect cancer earlier than current methods allow, which would increase the chances of a cure.

Since 2005, the unit she directed until January has provided genetic counseling to more than 5,000 patients and their families.

Urioste says that "it is not uncommon" for a case of hereditary cancer to go unnoticed by doctors in some public hospitals, partly because in Spain there is still no specialty in clinical genetics.

For his part, Villarroya points out that the study of this patient may reveal new ways of stimulating the immune system of patients so that it detects and eliminates tumors;

the basic mechanism of cancer immunotherapy treatments.

Ana Beatriz Sánchez Heras, a specialist in familial and hereditary cancer from the Spanish Society of Medical Oncology, who has not participated in the study, highlights its importance.

“It is a work that adds knowledge to the many mechanisms and molecular pathways that favor the malignant transformation of cells.

It will certainly have immediate clinical applications in the diagnosis and possibly treatment of cancers,” she says.

Jair Tenorio, a specialist in rare diseases of genetic origin at Hospital La Paz, in Madrid, and discoverer of Tenorio syndrome, highlights that this may be one of the people with the highest risk of known tumors in the world.

"I think we are facing a new disease," he says.

But the last word, he details, will be held by those responsible for the OMIM, the world's largest database of disorders of genetic origin.

Maybe they decide what to call it.

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