Researchers at Baylor College of Medicine and collaborators at other institutions have discovered that POT1 (protection of telomeres 1), a gene known to be associated with risk of glioma, the most common type of malignant brain tumor, mediates its effects in a sex-specific manner. The researchers found that female mice with glioma that lacked the gene survived less than males. This led them to investigate human glioma cells, where they found that low POT1 expression correlated with reduced survival in females. Published online on March 29, 2021 in Cancer Research, the study also shows that, compared to males, female tumors had reduced expression of immune signatures and increased expression of cell replication markers, suggesting that the immune response and tumor cell proliferation seemed to be involved in favoring tumor growth. The article is titled “POT1 Regulates Proliferation and Confers Sexual Dimorphism in Glioma” (https://cancerres.aacrjournals.org/content/early/2021/03/29/0008-5472.CAN-20-3755). This study began as a collaboration between Dr. Benjamin Deneen's lab at Baylor and Dr. Melissa Bondy's lab, previously at Baylor and now at Stanford University. Dr. Bondy and her group study familial or inherited forms of glioma from the epidemiologic standpoint. Their studies have linked mutations in the gene POT1 to the risk of glioma development. In the current study, the researchers looked to determine whether Pot1 mutations affected glioma development in a mouse model of the condition developed in the Deneen lab. "We began our study by knocking out the Pot1 gene in our mouse model and examining whether this affected the development and growth of glioma tumors," said first author Dr. Ali Jalali, Assistant Professor of Neurosurgery at Baylor. Dr. Jalali and his colleagues worked with male and female mice, and in their first analyses they pooled the data from both groups. "This analysis showed that the absence of Pot1 did not seem to affect tumor growth," Dr. Jalali said. "But then, a team member looked at male and female responses separately. Unexpectedly, we were able to see that in the absence of Pot1, gliomas grew faster in female mice. Females also had a shorter survival than males."
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