A woman who has developed twelve tumors, five of them malignant, over the course of her 36 years of life has become an exceptional case for science and opens new avenues of research against cancer.
Researcher Carolina Villarroya with Marcos Malumbres, head of the Cell and Cancer Division of the CNIO. / Laura M. Lombardy. CNIO. Photo provided
This woman had her first tumor process when she was almost a baby, and after that and every few years she developed other tumors, each one in a different part of the body and each one different from the previous one.
Researchers from the National Center for Oncological Research (CNIO) in Madrid have studied this exceptional case in depth and the results of their work are published in the journal Sciences Advances which specifies that the patient is a woman born in 1986.
CNIO scientists have discovered that the twelve tumors are because the patient inherited from both parents mutations in a gene essential for life.
He also has spots on his skin, microcephaly and other alterations.
Seconds Marcos Malumbres, head of the Cell and Cancer Division of the CNIO, “we still don’t understand how it was able to develop during its embryonic stage, nor how it was able to overcome all these pathologies”.
The study of this unique case opens, according to Malumbres, “a way to detect cells with tumor potential well in advance of clinical tests and imaging diagnosis; and also a new way to stimulate the immune response against a cancerous process”.
An essential gene in cell proliferation
When the patient first went to the Clinical Family Cancer Unit of the CNIO a blood sample was taken to sequence the genes most frequently involved in hereditary cancer, but no alterations were detected, and the researchers then analyzed his entire genome, and found mutations in one gene (called MAD1L1) .
This gene is essential in the process of cell division and proliferation, and the researchers analyzed the effect of the detected mutations and concluded that they cause alterations in the number of chromosomes in cells – all cells. cells in the human body have 23 pairs of chromosomes -.
In animal models it has been observed that when there are mutations in the two copies of this gene – each coming from one parent – the embryo dies; but, to the scientists’ surprise, the protagonist of this case has both mutated copies and has survived, leading a life as normal as his delicate health allows.
There is no other such case described, according to the researcher Miguel Urioste, who has led the Family Cancer Clinical Unit of the CNIO until retirement. “Academically you cannot speak of a new syndrome because it is the description of a single case, but biologically it is”.
Aggressive tumors disappear easily
One of the facts that most intrigued the research team was that the five aggressive tumors developed by the woman disappeared relatively easily.
Their hypothesis is that the constant production of cells with alterations has generated in the woman a chronic defensive response against these cells, and this helps to make the tumors disappear, so they have warned of the possibility that this could be useful for other patients: “by boosting their immune response we would help them slow down tumor development”, explained Malumbres.
To thoroughly study the patient and her relatives – several with mutations in the same gene, but only in one of the copies – the scientists used single cell analysis technology, which provides an “unthinkable” amount of information ” only a few years ago, the CNIO has highlighted.
It is about analyzing the genes “of each of the blood cells separately”, explained Carolina Villarroya-Beltri, CNIO researcher and first signatory of the study.
There are many different types of cells in the sample and generally all of them are sequenced, “but by analyzing thousands of these cells separately, one by one, you can study what happens in each cell. specific situation, and what are the consequences of these changes for the patient”, he specified.
Following their findings, the researchers propose in the paper that single-cell analysis can be used to identify cells with tumor potential long before clinical symptoms, or observable markers in analytical tests, appear. This study has opened new avenues for early diagnosis and immunotherapy to fight cancer.
The research has been coordinated by researchers Sandra Rodríguez-Perales, head of the CNIO Cytogenetics Unit; Marcos Malumbres, head of the Cell and Cancer Division of the CNIO; and Miguel Urioste, head of the Clinical Family Cancer Unit of the CNIO until retirement, and has had funds from the Ministry of Science and Innovation; the Scientific Foundation of the Spanish Association Against Cancer; and the Community of Madrid.