Original Academic Meridian
He is just 36 years old, but has already suffered from 12 types of tumors, the earliest of which appeared at the age of 2. Fortunately, the patient has responded well to many anti-cancer treatments and has not lost her life to cancer.
This experience sounds like a bit of a fantasy. What made this patient extremely susceptible to cancer and yet survive?
After many years, scientists finally discovered this patient's secret: this particular physique is associated with just one genetic mutation. According to a recent paper published in Science Advances, a woman who received a mutation from each of her parentsMAD1L1gene, resulting in aberrant MAD1 protein function.
The derangement of MAD1 is destructive to cell division. As we all know, an important step in mitosis is the orderly arrangement of the duplicated chromosomes in the midline of the cell, which is then equally distributed between the two new cells, and the MAD1 protein is supposed to ensure the correct arrangement of the chromosomes, so this patient with MAD1 derangement could easily experience a haphazard distribution of chromosomes.
According to blood sample testing, 30% to 40% of the patient's blood cells showed an abnormal number of chromosomes, too many or too few were present. In fact, in addition toMAD1L1Genetic mutations, and there have been many studies that have identified other genetic mutations affecting mitosis that can lead to significantly elevated cancer risk, and cells with abnormal chromosome counts are present in the vast majority of malignancies.
▲MAD1L1 mutation causes abnormal chromosome segregation (Image source: Reference )
Thus, in reviewing the history of this patient's hospitalization, it can be seen that she showed developmental delay and mild psychomotor suppression at one month of life. By the age of two, the cancer began to seek her out, when doctors found embryonal rhabdomyosarcoma in her ear canal, and subsequently administered chemotherapy and radiation therapy.
Due to premature exposure to radiation therapy affecting development, the patient had to receive additional growth hormone therapy to ensure normal growth.
Since then, patients have experienced a period of calm and quiet. However, at the age of 15, the tumor returned with a vengeance. Doctors detected the presence of chondrosarcoma in her femur and humerus, and clear cell cervical cancer was found that same year. In the years that followed, doctors also treated her for pleomorphic adenoma, spindle cell sarcoma, mammary lipoma, and trichoblastoma, and she was diagnosed with 12 different types of tumors, both benign and malignant, during her lifetime.
In 2014, she underwent her last cancer treatment, removing a tubular adenoma of the colon during a colonoscopy. Prior to that, doctors had also removed multiple tumor blocks in her colorectum. "It's hard to understand how this patient survived this mutation," said study corresponding author Dr. Marcos Malumbres, "There must have been some mechanism that helped her escape death."
Researchers tried to make mouse embryos carrying twoMAD1L1mutant copies, with the result that these mice die before they are born. For this patient, however, she survived despite being extremely susceptible to tumors.
Based on the analysis, the researchers found that despite the presence of chromosomally abnormal cells in the patient's body, other normal cells appear to have adapted to the situation, and they generate many defensive immune responses in response to the abnormality. Genes associated with inflammatory responses are upregulated in normal cells throughout the patient's body, including chemokines, and interferon signaling pathways, a move that enhances the activation of natural killer cells and T cells.
This systemic inflammatory response may be just what helps patients survive, clearing away most of the cancerous cells in time. A strong immune environment also enhances the effects of chemotherapy and radiation when the tumor grows out, ensuring that the cancer cells are removed.
"The patient developed a chronic immune response to these abnormal cells that helped stop the tumor from developing," Dr. Malumbres noted, adding that this patient's particular immune response may give ideas for other cancer treatments, especially by mimicking this type of immune pattern, and may be able to help cancer patients recover.