A woman who has been diagnosed with 12 tumors in her life has an unprecedented genetic mutation
The woman developed 12 tumors – seven benign and five cancerous – before her 40th birthday. Medical researchers recently discovered why she is so prone to abnormal growths: She carries a set of genetic mutations never before seen in humans.
The woman, now 36, carries two mutated copies of a gene called MAD1L1, one from each parent, according to a new report published Wednesday (November 2) in the journal Scientific progress (opens in a new tab). The gene encodes a protein called MAD1, which plays a key 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 center line of the cell and pull in half; that way, when a mother cell splits in 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 a new tab)a database of protein sequences and functional information.
When laboratory mice carry two mutated copies of MAD1L1, the rodents die in utero. However, in the case of the woman, she survived into adulthood but was extremely susceptible to tumors throughout her life. She got her first cancerous tumor at the age of 2, and the last one at the age of 28.
“It was very difficult to understand how this woman could survive with this mutation,” the co-author Marcos Malumbres (opens in a new tab)head of the cell division and cancer group at Spain’s National Cancer Research Center (CNIO) in Madrid, told a Spanish newspaper Earth (opens in a new tab). “There had to be something else that helped her escape [death]”, Malumbres said, as translated by Live Science.
Analysis of the patient’s blood revealed that about 30% to 40% of her circulating blood cells carried an abnormal number of chromosomes—either 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% of cancerous tumors contain cells with extra or missing chromosomes, according to National Cancer Institute (opens in a new tab); however, scientists are still investigating exactly how this genetic flaw contributes to the growth and spread of cancer.
Despite being diagnosed with cancer five times, the patient was relatively easily treated each time she developed the disease. And since her last tumor was removed in 2014, the patient has not developed another one. Medical researchers think this may be due to her uniqueness immune system.
In their analyses, the team found that the presence of cells with an abnormal number of chromosomes triggered a defensive immune response in cells with the typical 23 pairs. These immune cells trigger inflammation throughout a woman’s body, and by releasing specific molecules and inflammatory substances, the cells can help the immune system spot and destroy cancer tumors when they appear. This may explain why the patient responded well to cancer treatment, including chemotherapy, radiotherapy and surgery, the team theorizes.
“The constant production of altered cells created a chronic defensive response in the patient against these cells, and this helps the tumors to disappear,” Malumbres said in statement (opens in a new tab). The team hopes to further study the woman’s immune defenses to see if they can recreate them in other cancer patients.
“We think that boosting the immune response of other patients would help stop the tumor from developing,” Malumbres said. Conceptually at least, such a treatment would be similar to existing immunotherapies designed to boost the immune system’s ability to target and kill cancer cells.