Woman has 12 tumors at age 30 due to one-of-a-kind genetic mutation

An extremely rare and never-before-seen genetic disease caused a Spanish woman to develop 12 different types of tumors before the age of 30, according to the authors of a new study. Now 36, the patient has been disease-free since 2014, when a tumor was surgically removed from her colon.

Born in 1986, the patient first underwent chemotherapy at age 2 for left ear canal sarcoma, and continued to suffer from a new tumor every few years. Remarkably, each subsequent disease was of a different type and occurred in a different part of the body, with at least five of the 12 malignancies.

In 2017, researchers examined the woman for genes that are commonly associated with hereditary cancer, but found no risk factors. However, an analysis of the subject’s entire genome revealed something truly amazing: the two copies of a gene called MAD1L1 were found to carry a mutation.

MAD1L1 codes for a protein called MAD1, which plays a role in regulating cell division and proliferation. We all inherit two copies of this gene – one from each parent – and although it is possible for a person to carry a mutation in one of them, embryos that inherit two mutated copies always die in the process. ‘uterus.

Commenting on the woman’s remarkable condition in a statement, study author Marcos Malumbres said “we still do not understand how this individual was able to develop in the embryonic stage, or overcome all these pathologies.”

Describing the effects of these mutations, the researchers reveal that dysregulated cell proliferation resulted in 30-40% of female blood cells carrying the wrong number of chromosomes. Under normal circumstances, all human cells have 23 pairs of chromosomes, although this is sometimes altered in people with a condition called mosaic variegated aneuploidy (MVA).

Since the majority of cancer cells have extra or missing chromosomes, people with MVA may be more susceptible to disease. Birth defects and learning disabilities are also common in people with aneuploidy, although the study authors say the patient had no intellectual disability.

However, she had a number of physical symptoms, including microcephaly, an underdeveloped jaw and eye sockets, and nystagmus – which is characterized by repeated involuntary eye movements. Despite these genetic abnormalities, the study authors claim that the woman was able to lead a normal life, although she was severely affected by repeated illnesses.

Amazingly, this is the first time scientists have seen a living person with two mutated copies of the MAD1L1 embarrassed. Commenting on the uniqueness of the condition of women, the author of the study, Miguel Urioste, explained that “academically, we cannot speak of a new syndrome because it is the description of ‘only one case, but biologically it is’.

Aneuploidy itself is not unheard of, with Down syndrome being the most common form of the condition. However, says Urioste, “this case is different in aggressiveness, the percentage of aberrations it produces, and the extreme susceptibility to a large number of different tumors”.

In another incredible twist, the same condition that causes the woman’s susceptibility to cancer also appears to help her recover from the disease. Noting the relative ease with which she continually overcame the disease, the researchers believe that her immune system may have developed the ability to target and destroy aneuploid cancer cells.

Since most cancer cells are indeed aneuploid, the study authors say a better understanding of the woman’s condition could provide clues as to how other patients’ immune systems may be boosted. to destroy tumors.

The study was published in the journal Science Advances.

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