Genetic Mutation vs Amplification: When Does It Matter?

Maurie Markman, MD


October 31, 2013

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Hello. This is Dr. Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a very interesting topic that has probably been considered by many oncologists in this new world of genomic medicine: the difference between a molecular test stating that a particular gene is amplified vs a particular gene being mutated. Are they the same or different in terms of therapeutic implications?

Amplification implies that you have a normal gene, but there is much more of it. For example, when we talk about HER2 overexpression in breast cancer, that is a normal HER2 gene, but there is much more of it. This, of course, has important prognostic and therapeutic implications because there are drugs that can block the HER2 receptors.

So, overexpression -- or more of it -- is one possible abnormality. But a second possible abnormality is that you have a gene that you might see the same amount of, but there is a specific mutation within the normal gene.

Are those two the same, or are they always different?

It's hard to answer the question definitively, but there is a recent paper looking at melanomas and specifically at a particular gene known as KIT and whether a mutation in KIT or amplification of KIT makes a difference [in treatment response].

In this paper, published in the Journal of Clinical Oncology and titled, "Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising in Mucosal, Acral, and Chronically Sun-Damaged Skin," it was shown that in 7 of 13 -- 54% -- of tumors in which KIT was mutated, there was a response, whereas in the population that had amplification of KIT, there were no responses.[1]

This was a small patient population, but there is clear evidence that mutation is not the same thing as amplification. We are going to have to learn more about these particular abnormalities, and clearly it is not as simple as saying, well, there is an abnormality in KIT. You have to know many more details. In this evolving world of genomic medicine -- or precision medicine -- we are going to have to learn more about how to optimally treat our patients based on the various specific abnormalities seen.

I thank you for your attention.


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