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Genetic fingerprinting used to confirm maternal spread of leukemia

10/20/2009
Erin Podolak

Scientists have confirmed that leukemic cells in a Japanese infant are of maternal origin.

Scientists have long been perplexed by rare cases of mothers and their infants developing the exact same cancer. Accepted biological theories dictate that the immune system of the infant would fight off maternal cancer cells as foreign bodies. However, British scientists from the Institute of Cancer Research (ICR) have used advanced genetic fingerprinting to confirm a maternal link in the spread of leukemia.

On Oct. 12, scientists from ICR announced the results of a study that used advanced genetic fingerprinting technology to evaluate the origin of leukemic cells in a Japanese infant. The scientists confirmed the cells spread to the infant through the womb of the child’s mother. Genetic fingerprinting makes use of restriction endonucleases, which cut strands of DNA at specific locations determined by the exact order of the four DNA bases. Genetic differences between individuals lead to variations in the length of the resulting DNA fragments. These fragments are separated by electrophoresis and visualized in a profile—known as a DNA fingerprint—and then analyzed.

The study revealed that both the infant and its mother carried leukemic cells with the identical mutated cancer gene BCR-ABLI. Since the mutation was not hereditary, the child did not have the mutated gene because it had been genetically inherited from its mother. However, because the mutation was identical in mother and child, the infant had to acquire the mutation from its mother in some way. Mel Greaves, professor of cell biology at ICR, said the cancer cells moved into the child while it was in the womb. “It appears that in this and, we presume other cases of mother to offspring cancer, the maternal cancer cells did cross the placenta into the developing fetus and succeeded in implanting because they were invisible to the immune system,” said Greaves in a press release.

ICR stated that prior to their research, there were 30 known cases of a mother and infant appearing to share the same cancer (leukemia or melanoma); however, there was no genetic evidence to support the theory that the cancerous cells were crossing into the fetus in utero. According to Greaves, scientists were puzzled by the trend because a baby’s immune system should recognize and destroy any invasive maternal cancer cells because they are foreign bodies.

The researchers looked for evidence of immunological acceptance of the foreign cells by the infant to explain why it was possible for the cancerous cells to cross the placental barrier and implant in the fetus. The researchers used genetic fingerprinting to identify a deletion mutation in the infant in the genetic region that controls expression of the major histocompatibility locus (HLA.) According to ICR, this was significant because HLA molecules distinguish the cells of individuals from each other. This indicates that the absence of these molecules on the infant’s cancer cells allowed the cells to be accepted by the infant’s immune system.

Greaves said that while the research does confirm that passing cancerous cells from mother to infant is possible, it is still extremely rare. “We are pleased to have resolved this longstanding puzzle,” said Greaves in a press release, “but we stress that such mother-to-offspring transfer of cancer is exceedingly rare and the chances of any pregnant woman with cancer passing it on to her child are remote.”

The study, “Immunologically silent cancer clone transmission from mother to offspring” was published in the Oct.12 edition the Proceedings of the National Academy of Sciences. Funding was provided by Leukemia Research, the Kay Kendall Leukemia Fund, and the ICR.