Scientists identify molecular biomarker for malignant melanoma

By John Murphy, MDLinx
Published September 8, 2016

Key Takeaways

Scientists in Spain have discovered that partial loss of the ATG5 autophagy gene is a distinctive feature of advanced melanomas—and this feature could be used as a molecular biomarker of melanoma progression, according to their study published August 27, 2016 in Autophagy.

Notably, partial ATG5 loss predicts poor overall patient survival—tumors become more metastatic and more resistant to therapies that target melanoma, the researchers found. These findings support the use of the ATG5 protein as a molecular marker of the metastatic potential of melanomas, which are currently diagnosed largely by histopathological criteria, such as measuring tumor thickness.

In this study, researchers at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain, analyzed about 20 autophagy genes in more than 25 types of cancer using data derived from nearly 5,000 patients.

“We proved a huge variability between the different types of tumors. However, we found alterations in the ATG5 gene that only provided diagnostic value in melanoma,” said lead researcher María S. Soengas, PhD, head of the CNIO’s Melanoma Group.

Dr. Soengas and colleagues demonstrated that melanoma cells limit ATG5 levels in a very specific way: by selectively losing one of the copies of the ATG5 gene. They also learned that this process doesn’t occur in other autophagy factors.

To study ATG5 in vivo, the researchers deleted one of the copies of the ATG5 gene in genetically-modified mice. “We discovered that when tumors lose only one copy of ATG5, they not only become more aggressive and metastatic, but also respond worse to current drugs used for targeted therapies in melanoma,” Dr. Soengas explained.

She added that this discovery will greatly enhance clinicians’ ability to identify the risk of disease progression and predict a patient’s prognosis, and also improve patient monitoring. But it also raises a red flag for drug therapy because it suggests that partial blockage of the ATG5 gene could unexpectedly worsen the malignant behavior of metastatic melanomas.

This discovery also lights the way for researching less common and less-studied melanomas, such as ocular or mucous melanomas, Dr. Soengas predicted.

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