One woman developed 12 tumors — seven benign and five cancerous — before her 40th birthday. Medical researchers recently discovered why she is so prone to the abnormal growths: She carries a set of genetic mutations never before seen in humans.
The woman, now 36, carries two mutant copies of a gene called MAD1L1, one from each parent, according to a new report published Wednesday (Nov. 2) in the journal Scientific progress (opens in new tab). The gene encodes a protein called MAD1 that plays a crucial role in cell division.
When a cell divides into two, it first duplicates all of its own DNA and then packages the genetic material into compact structures called chromosomes. The chromosomes then line up neatly along the midline of the cell and are torn in half; thus, when the mother cell divides into two, half of the DNA ends up in each daughter cell. The protein MAD1 helps ensure that the chromosomes line up correctly during this process, so that all cells end up with the usual 23 pairs of chromosomes, according to UniProt (opens in new tab)database of protein sequence and functional information.
When laboratory mice carry two mutant copies of MAD1L1, the rodents die in utero. However, in the woman’s case, she survived into adulthood but was extremely susceptible to tumors throughout her life. She developed her first cancer at age 2 and her last at age 28.
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“It was very difficult to understand how this woman could survive with this mutation,” co-senior author Marcos Malumbres (opens in new tab)head of the Cell Division and Cancer Group at the Spanish National Cancer Research Center (CNIO) in Madrid, told the Spanish newspaper The country (opens in new tab). “There had to be something else that helped her escape [death]Malumbres said, according to a Live Science translation.
An analysis of the patient’s blood revealed that about 30% to 40% of her circulating blood cells carried an abnormal number of chromosomes—too many or too few.
Genetic mutations other than those affecting MAD1L1 can cause people to carry cells with different numbers of chromosomes. In some patients, but not all, it appears to increase the risk of cancer, the researchers noted in their report. About 90 percent of cancer tumors carry cells with extra or missing chromosomes, according to the National Cancer Institute (opens in new tab); however, scientists are still investigating exactly how this genetic quirk contributes to the growth and spread of cancer.
Although she had cancer five times, the patient was treated relatively easily each time she developed the disease. And since her last tumor was removed in 2014, the patient has not developed another. Medical researchers believe this may be due to her uniqueness immune system.
In their analyses, the team found that the presence of cells with an unusual number of chromosomes triggered a protective immune response in cells with the typical 23 pairs. These immune cells rule inflammation throughout a woman’s body, and by releasing specific molecules and inflammatory substances, the cells can help the immune system spot and destroy cancerous tumors when they arise. This could explain why the patient responded well to cancer treatments, including chemotherapy, radiation therapy and surgery, the team theorized.
“The constant production of altered cells has generated a chronic protective response in the patient against these cells, and this helps the tumors disappear,” Malumbres said in statement (opens in new tab). The team hopes to study the woman’s immune defenses further to see if they can recreate it in other cancer patients.
“We think that boosting the immune response of other patients would help them stop the tumor from growing,” Malumbres said. At least conceptually, such a treatment would be similar to existing immunotherapies designed to boost the immune system’s ability to target and kill cancer cells.