When scientists in Spain discovered the strange case of a woman who had 12 different types of tumors before the age of 36, they decided to dig a little deeper to find out why she was so susceptible to cancer.
The 36-year-old was first treated for cancer when she was two years old. At the age of 15, she was diagnosed with cervical cancer.
At age 20, a salivary gland tumor was surgically removed. A year later, she underwent further surgery to remove a low-grade sarcoma.
And, as she passed through her 20s and 30s, several different tumors were diagnosed.
In total, she suffered 12 tumors, five of which were malignant.
With the permission of the woman and her family, an international team of researchers, led by Spain’s National Cancer Research Center, took blood samples and used single-cell DNA sequencing to examine genetic mutations in inside thousands of individual cells.
Researchers have discovered something strange; this woman had a one-of-a-kind mutation that made her more prone to cancer.
She had a mutation in both copies of the MAD1L1 gene, which is unknown in humans.
The MAD1L1 gene is responsible for a key piece of machinery that helps align chromosomes before a cell divides. MAD1L1 has previously been suspected of playing a role in tumor suppression.
Mutations in the gene are not unheard of – in fact, the woman’s family members carried them. But this is the first time that both copies of the gene have carried this particular change.
A double (or homozygous) mutation in the MAD1L1 gene is lethal to mouse embryos, so this is a very surprising finding in humans.
In this woman, the mutation caused cell replication to malfunction and created cells with a different number of chromosomes. About 30-40% of his blood cells had an abnormal number of chromosomes.
Humans normally have 23 pairs of chromosomes inside the nucleus of every cell in our body.
Chromosomes are condensed packages of DNA that are shaped like an “X” and form when a cell is about to undergo mitosis or cell replication.
In each pair of chromosomes, one comes from the person’s mother and the other comes from the person’s father.
People with a rare condition called “mosaic variegated aneuploidy” (MVA) have varying numbers of chromosomes in different cells, like a mosaic of differently colored tiles. This condition can be caused by several different genetic mutations, including the one seen in women with 12 cancers.
People born with MVA often have developmental delay, microcephaly (where a child’s head is smaller than normal), intellectual disability, and other birth defects. They are often predisposed to cancer.
In this case, the woman had no intellectual disability and was living a relatively normal life (considering the number of rounds of cancer treatment she had undergone).
“We still do not understand how this individual was able to develop at the embryonic stage, nor overcome all these pathologies”, explains Marcos Malumbres, molecular biologist, co-author and head of the Cell Division and the Cancer Group at the Institute National Center Spanish Cancer Research Center, where this study was carried out.
Although the role of aneuploidy is not well understood in cancer, we know that approximately 90% of tumors contain cancer cells with extra or missing chromosomes.
And we know that a high degree of aneuploidy is associated with poorer cancer outcomes.
The study found that people with aneuploidy, like this woman in the case study, have an “enhanced immune response” that “could provide new opportunities for the clinical management of these patients,” say the researchers. researchers.
This article was published in Scientific advances.