Genetic Mutation, A woman developed 12 tumors — seven benign and five cancerous — before her 40th birthday. Medical researchers recently discovered why she’s so prone to abnormal growths: She carries a set of genetic mutations never seen before in humans.
The woman, now 36 years old, 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 Science Advances (opens in new tab). The gene codes for a protein called MAD1, which fulfills a crucial role in cell division.
When one cell splits into two, it first duplicates all its DNA and then packages the genetic material into compact structures called chromosomes. The chromosomes then line up neatly along the cell’s midline and get yanked in half; that way, when the mother cell splits in two, half of the DNA ends up in each daughter cell. The MAD1 protein helps ensure that the chromosomes line up correctly during this process, so all cells end up with the usual 23 pairs of chromosomes, according to UniProt (opens in new tab), a database of protein sequence and functional information.
When lab mice carry two mutant copies of MAD1L1, the rodents die in the womb. However, in the woman’s case, she’s survived into adulthood but has been extremely susceptible to tumors throughout her life. She developed her first cancerous tumor at age 2 and her most recent one 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 El País(opens in new tab). “There had to be something else that had helped her escape [death] ,” Malumbres said, according to a translation by Live Science.
An analysis of the patient’s blood revealed that about 30% to 40% of her circulating blood cells carry an abnormal number of chromosomes — either too many or too few.
Other genetic mutations besides those affecting MAD1L1 can cause people to carry cells with different numbers of chromosomes. In some patients, but not all, this seems to raise the risk of cancer, the researchers noted in their report. About 90% of cancerous 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 cancer’s growth and spread.
Despite having 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 hasn’t developed another. The medical researchers think this may be thanks to her unique immune system.
In their analyses, the team found that the presence of cells with abnormal numbers of chromosomes kicked off a defensive immune response in cells with the typical 23 pairs. These immune cells drive inflammation throughout the woman’s body, and by spewing specific molecules and inflammatory substances, the cells may help the immune system spot and destroy cancerous tumors when they arise. This may explain why the patient responded well to cancer treatments, including chemotherapy, radiotherapy, and surgeries, the team theorizes.
“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,” Malumbres said in a statement (opens in new tab). The team hopes to study the woman’s immune defenses further, to see if they could recreate them in other cancer patients.
“We think that boosting the immune response of other patients would help them to halt the tumoural development,” 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.