New! Sign up for our free email newsletter.
Science News
from research organizations

It takes more than one mutant copy of the PIK3CA gene to make breast cancer more aggressive, study finds

Date:
November 11, 2021
Source:
PLOS
Summary:
Breast cancers that have an overactive PI3K enzyme tend to be more aggressive and to spread and divide more like stem cells. But a new study uncovers a surprising relationship between PI3K activity and mutations in the PIK3CA gene that codes for the enzyme.
Share:
FULL STORY

Breast cancers that have an overactive PI3K enzyme, involved in cell growth and division, tend to be more aggressive and to spread and divide more like stem cells. But a new study by Ralitsa Madsen of University College London and colleagues publishing Nov. 11 in the journal PLOS Genetics uncovers a surprising relationship between PI3K activity and mutations in the PIK3CA gene that codes for the enzyme. Breast cancer tumors with one mutant copy of the PIK3CA gene tend to have lower PI3K activity. In comparison, patients with two or more copies often had higher PI3K? activity, resulting in more aggressive tumors and a poorer prognosis for patients with certain types of breast cancer.

Experiments in the lab previously showed that two but not one mutant PIK3CA gene can promote a persistent stem cell state -- a quality called "stemness." But until now, there was no evidence from human patients to support this idea. In the new study, researchers investigate the relationship among PI3K mutations, PI3K activity and stemness in breast cancer. They used publicly available data from nearly 3,000 breast cancer tumors and applied computational methods to infer PI3K activity and stemness. They discovered that aggressive tumors had more PI3K activity and a higher degree of stemness. However, they were surprised to find that cancer cells with only one mutant copy of PIK3CA had lower levels of stemness and are potentially less aggressive.

The new study supports the idea that overactive PI3K enzymes are linked to more aggressive breast cancers. Additionally, the researchers warn that the number of copies of mutant PIK3CA mutations in a tumor may affect how it responds to cancer therapies. They conclude that this information, along with data on PI3K activity, should be considered when choosing patients to participate in clinical trials of new drugs.

Madsen adds, "Breast cancer stratification by PIK3CA mutant dose reveals a counterintuitive relationship with functional indices of PI3K pathway activity and tumor dedifferentiation."


Story Source:

Materials provided by PLOS. Note: Content may be edited for style and length.


Journal Reference:

  1. Ralitsa R. Madsen, Emily C. Erickson, Oscar M. Rueda, Xavier Robin, Carlos Caldas, Alex Toker, Robert K. Semple, Bart Vanhaesebroeck. Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype. PLOS Genetics, 2021; 17 (11): e1009876 DOI: 10.1371/journal.pgen.1009876

Cite This Page:

PLOS. "It takes more than one mutant copy of the PIK3CA gene to make breast cancer more aggressive, study finds." ScienceDaily. ScienceDaily, 11 November 2021. <www.sciencedaily.com/releases/2021/11/211111154249.htm>.
PLOS. (2021, November 11). It takes more than one mutant copy of the PIK3CA gene to make breast cancer more aggressive, study finds. ScienceDaily. Retrieved April 20, 2024 from www.sciencedaily.com/releases/2021/11/211111154249.htm
PLOS. "It takes more than one mutant copy of the PIK3CA gene to make breast cancer more aggressive, study finds." ScienceDaily. www.sciencedaily.com/releases/2021/11/211111154249.htm (accessed April 20, 2024).

Explore More

from ScienceDaily

RELATED STORIES