MADRID, Spain — A unique patient who has survived the development of a dozen tumors could hold the key to curing cancer, a new study reveals.
Their review found that the individual is “programmed” to develop different forms of the disease after inheriting mutations in a gene from both parents. However, their immune system naturally generates a strong anti-inflammatory response that fights the growths. Knowing how it does this offers a “groundbreaking” hope of earlier disease diagnosis and new immunotherapy drugs.
“We still don’t understand how this individual could have developed during the embryonic stage, nor could have overcome all these pathologies,” says Marcos Malumbres, head of the Cell Division and Cancer Group at the Spanish National Cancer Research Centre (CNIO), in a media release.
The unnamed patient around the age of 40 has had 12 tumors, with at least five of them being malignant. The first developed during infancy, followed by others every few years. Each has been of a different type and in a different part of the body. The patient also has skin spots, the birth defect microcephaly which causes a smaller head and brain, and other alterations.
According to Malumbres, the study of this unique case opens up “a way to detect cells with tumor 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.”
This unique case focuses on one gene
Mapping the individual’s entire genome identified mutations in a gene called MAD1L1. It’s essential in the process of cell division and proliferation. Analyses showed the variants alter the number of long strands of DNA in cells, known as chromosomes. There should be 23 pairs in the human body.
In animal models, scientists have observed that when there are mutations in both copies of the gene, one coming from each parent, the embryo dies. To the astonishment of the team, the patient has survived, living as normal a life as can be expected of someone suffering from ill health.
The case described in the journal Science Advances is understood to be unique in the medical literature.
“Academically we cannot speak of a new syndrome because it is the description of a single case, but biologically it is,” says Miguel Urioste, the former head of CNIO’s Familial Cancer Clinical Unit.
Studies have found other genes whose mutations change the number of chromosomes. However, this case is different because of its aggressiveness, the percentage of aberrations it produces, and the extreme susceptibility to a large number of different tumors. Moreover, the five aggressive cancers the patient developed 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 tumors to disappear,” explains Malumbres. “We think that boosting the immune response of other patients would help them to halt the tumoral development.”
The discovery could create a new tumor-killing treatment
Discovering the immune system is capable of unleashing a defensive response against cells with the wrong number of chromosomes is potentially groundbreaking. Malumbres calls this “one of the most important aspects of this study, which may open up new therapeutic options in the future.”
In human tumors, 70 percent have cells with an abnormal number of chromosomes. Several relatives of the patient also have mutations in the MAD1L1 gene, but only in one of the copies. The researchers used a state-of-the-art technique called single-cell analysis which provides a wealth of information. It involves scanning the genes of each of the blood cells separately.
“By analyzing thousands of these cells separately, one by one, we can study what is happening to each specific cell, and what the consequences of these changes are in the patient,” says study first author Dr. Carolina Villarroya-Beltri.
The blood sample contained several hundred chromosomally identical immune cells, called lymphocytes, coming from a single, rapidly proliferating source. They attack specific invaders, but sometimes they proliferate too much and spread to form a tumor.
The original stages of a cancer were being captured by this work. So, single-cell analysis identifies tumor cells years before the appearance of clinical symptoms.
South West News Service writer Mark Waghorn contributed to this report.