Credit: Juha Klefstrom
Investigators have identified biological signatures in lymphoma cells that can be traced back to the original oncogene.
The team analyzed mouse models and patient samples of MYC-induced lymphoma. And they discovered lipid signatures that corresponded with the level of MYC expression.
The investigators believe this discovery could be the first step toward developing a technique to identify the origin of lymphomas and other malignancies.
They described their discovery in PNAS.
“The same cancer can occur because of different genes, but, in certain cases, the aggressiveness and the type of treatment actually depend a lot on what oncogene caused that cancer,” said study author Livia Eberlin, PhD, of Stanford University in California.
With that in mind, she and her colleagues looked at MYC, an oncogene that’s responsible for approximately half of all human cancers. They wanted to find a biological signature that would trace the mutating cancer cells back to the original oncogene.
“When cancer takes place, the cell loves to gobble up glucose—that’s a sugar—and glutamine,” said Richard Zare, PhD, also of Stanford. “It takes those and makes different lipids—different fatty molecules than what it normally makes.”
So the investigators set out to evaluate changes in lipid profiles in MYC-induced lymphoma. They compared lipid signatures in MYC-induced transgenic mouse models to those in normal control mice.
The team identified 104 molecular ions that were either increased or decreased in the MYC lymphoma models compared to controls. And 86 of these ions were complex phospholipids.
Most of the lipids that were increased in lymphoma were glycerophosphoglycerols and cardiolipins, with a higher content of monounsaturated fatty acids when compared with controls.
To determine if these findings might also apply to humans, the investigators examined 15 samples from lymphoma patients.
The samples had varying expression levels of MYC oncoprotein, and the team observed distinct lipid profiles in lymphomas with high and low MYC expression. This included many of the lipid species they had identified in the animal models of MYC-induced lymphoma.
The investigators said their results suggest a relationship between specific lipid species and the overexpression of MYC. And this information could have both diagnostic and prognostic applications.
