Cancer Jackpot

The chance of cancer recurring in a person’s body is extremely small. According to Livestrong, a foundation that supports cancer survivors, one to three percent of cancer survivors may have a second, unrelated case of cancer (“Second Cancers”). The risk is low, and with advancements in medical care, more survivors live longer without developing another case of cancer. However, a woman broke all the odds. At the age of two, the woman began receiving cancer treatment when she tested positive for cancer (Lanese). Then, when she was 15 years old, she was diagnosed with cervical cancer. At 20, she had surgery to remove a salivary gland tumor and underwent another surgery a year later to remove a small tumor. Before turning 40, the woman had 12 tumors, five malignant and seven benign. It was reported that she has since turned 36 years and has not developed another case of cancer since 2014 (Lanese). Clearly, deeper investigation into this rare case of cancer would be needed for scientists to fully understand how cancer could reoccur this frequently in the span of 36 years. An international study team, coordinated by the Spanish National Cancer Research Center, obtained blood samples, with the woman’s consent, and utilized single-cell DNA sequencing to look at the genetic changes within thousands of single cells (Nelson). After a thorough examination of her DNA, medical researchers recently discovered the reason why she is highly susceptible to cancer. She carries a set of genetic mutations never seen in humans before. According to the journal Science Advances, the woman carries two mutant copies of a gene called MAD1L1, one from each parent (Villarroya-Beltri). When a single cell divides into two, it copies all of its DNA before packing the genetic information into little units called chromosomes. Then, when the mother cell divides into two, the chromosomes line up perfectly along the midline and are torn in half, distributing half of the DNA into each daughter cell. All cells end up with the typical 23 pairs of chromosomes as a result of the assistance provided by the MAD1L1 protein when aligning up the chromosomes. Scientists suspect that the MAD1L1 aids in tumor suppression. Although the MAD1L1 has a significant benefit in aiding a person’s immune system, there are also negative effects of having two mutant copies of the protein: studies have shown that laboratory mice that have two copies of MAD1L1 die in the womb, and this also applies to human beings. In this case, the woman was able to live to maturity, yet she still has a high propensity for cancer malignancies. Marcos Malumbres, a co-senior author and director of the Cell Division and Cancer Group at the Spanish National Cancer Research Center (CNIO) in Madrid, told the Spanish daily El Pas that it was "extremely difficult to explain how this woman could survive with this mutation" (Domínguez). The analysis of the woman’s blood showed that approximately 30-40% of the woman’s circulating blood cells have an abnormally high or low number of chromosomes. Researchers found that people can have cells with variable numbers of chromosomes due to genetic mutations, other than those that affect MAD1L1, and this appears to increase the likelihood of developing cancer (Domínguez). According to the National Cancer Institute, almost 90 percent of malignant tumors contain cells with extra or absent chromosomes (Jaber). Unfortunately, it is unclear exactly how this genetic anomaly affects the development and progression of cancer. The woman was treated quite readily each time she had cancer, and she has been tumor-free since her last one was removed in 2014. Medical specialists conclude that she may have developed a special immune system that helps prevent the growth of cancer in her body.

With a detailed analysis of the woman’s genetic mutation, the team revealed that the cells with the conventional 23 pairs of chromosomes began to mount a protective immune response in the presence of cells with abnormally high numbers of chromosomes (Lanese). By spreading certain chemicals and inflammatory compounds throughout the woman’s body, the immune cells can identify and eliminate malignant tumors when they develop. This is also why the patient reacted well to all the cancer treatments, including chemotherapy, radiation, and surgery. Malumbres stated that “the continuous creation of altered cells has developed a persistent defensive reaction in the patient against these cells, and that assists the tumors to go away” (Domínguez). The team wants to learn more about the woman’s immune system in hopes that they can duplicate her immune cells to treat other cancer patients. Since there is only one known case at this time, the team has not yet given the patient's condition a new name. Instead, it is now part of the mosaic-variegated aneuploidy syndrome (MVA), a collection of uncommon genetic diseases (Domínguez). Only three genes were known to induce MVA up until this point. People with MVA are more likely to get cancer and may experience one or two malignancies during their lifetimes. However, the MAD1L1 mutation, the fourth gene linked to MVA, causes more cases of cancer than the other three (Domínguez). Therefore, it is important to understand the factors that trigger MAD1L1 and know how to treat them properly. By studying the unique immune system, doctors hope to find the treatment for cancer for the future generation, allowing cancer patients to be treated more quickly and effectively.

References

Domínguez, Nuño. “Unique Case of Woman Who Survived 12 Tumors May Indicate ‘New Disease’.” El Pais. 3 Nov. 2022. english.elpais.com/science-tech/2022-11-03/unique-case-of-woman-who-survived-12-tumors-may-indicate-new-disease.html#:~:text=A%20Spanish%20woman%20who%20overcame,development%20of%20new%20cancer%20treatments. Accessed 22 Nov. 2022

Jaber, Nadia. “Extra or Missing Chromosomes May Help Cancer Cells Survive Treatment.” National Cancer Institute. 24 Sep.2021. www.cancer.gov/news-events/cancer-currents-blog/2021/aneuploidy-cancer-treatment-resistance. Accessed 22 Nov. 2022.

Lanese, Nicoletta. “Woman Diagnosed With 12 Tumors In Her Lifetime Has a Never-Before-Seen Genetic Mutation.” LiveScience. 6 Nov. 2022. www.livescience.com/woman-with-genetic-mutation-tumor-prone. Accessed 22 Nov. 2022.

Nelson, Felicity. “A Woman Had Cancer 12 Times by Age 36. Her Genes Showed Something Never Seen Before.” Science Alert. 4 Nov. 2022. www.sciencealert.com/a-woman-had-cancer-12-times-by-age-36-her-genes-showed-something-never-seen-before. Accessed 22 Nov. 2022.

“Second Cancers.” LiveStrong. www.livestrong.org/we-can-help/healthy-living-after-treatment/second-cancers Accessed 22 Nov. 2022.

Villarroya-Beltri, Carolina. “Biallelic Germline Mutations in MAD1L1 Induce a Syndrome of Aneuploidy with High Tumor Susceptibility.” Science Advances. 2 Nov. 2022. www.science.org/doi/10.1126/sciadv.abq5914?cookieSet=1 Accessed 22 Nov. 2022.