New ideas for cancer therapy targeting mutant p53: consider the role of chromosomal changes

The tumor suppressor protein p53 is mutated in more than half of human cancers

However, there is still much to be understood about the various mutations that cause the "loss of function" of proteins and other mutations that lead to the "gain of function" presumed to be malignant, such as the acceleration of cancer growth and spread (metastasis)

Some studies have observed a positive correlation between p53 mutations and aneuploidy.

Now, researchers at Vanderbilt University Medical Center have discovered that in cells expressing mutant p53, aneuploidy drives the function to acquire a phenotype

"The concept of mutant p53 gaining function was introduced more than 30 years ago.

Pietenpol is the Benjamin F.

In the current study, the researchers used CRISPR-Cas9 gene editing technology to develop two genetically identical epithelial cell line models containing p53 mutations

They found that the gain-of-function phenotype in vitro was only in cell lines that showed increased aneuploidy

Therefore, the researchers concluded that addressing the functional gain of mutant p53 must take into account the effects of chromosomal changes