What causes ALK+ lung cancer?

Someone recently posted this question on Inspire.com. Here was my reply.

I have wondered about this for a while. I recently found some information others may find interesting. I do not know if any of the following applies to ROS+ patients.

EML4-ALK and NPM-ALK are both fusion genes, which are a different kind of genetic alteration than the type of mutation people usually think of (I am not sure it is even proper to refer to it as a mutation and have noticed several research articles seem to go out of their way to avoid that term). A “typical” mutation involves the addition, deletion, or changing of one or more base pairs (G, A, C, T) on the DNA strand. Now some patients with familial cases of neuroblastoma appear to have ALK “mutations” that can be inherited from parents, but these cases are rare.

By contrast, fusion genes are caused by chromosome translocations or inversions (see http://en.wikipedia.org/wiki/Fusion_gene). Fusion genes involve the combining of parts of two different genes (for more info on chromosome translocations see http://en.wikipedia.org/wiki/Chromosomal_translocation ). Apparently, many fusion genes are oncogenes (genes that cause cancer). The two genes that form the fusion gene may come from different chromosomes. In the case of NPM-ALK they are chromosomes 5 and 2 respectively. In the case of EML4-ALK the two genes are both found on chromosome 2. It appears that different cancer types (for example ALK+ lung cancer or anaplastic large-cell lymphoma) are usually caused by one type of fusion gene (for example EML4-ALK or NPM-ALK).

Here is a 2008 Nature.com article (http://www.nature.com/scitable/topicpage/human-chromosome-translocations-an d-cancer-23487 ) about chromosome translocations in general.

Both the Wikipedia page on chromosome translocation and the Nature article mention that early research (as early as 1938) suggested that exposure to “ionizing radiation” (including X-rays, radioactive materials, and cosmic rays) and the creation of “free radicals” (see http://en.wikipedia.org/wiki/Ionizing_radiation) greatly increased the likelihood of chromosome translocations. Neither source goes into other potential causes of chromosome translocations. Perhaps further research since 2008 (or 1938) has found other potential causes for chromosome translocations (I have yet to find them).

It sounds to me like some relevant risk factors might include: getting X-ray images of teeth or broken bones, flying on airplanes regularly, and being exposed to radioactive materials.

I hope people find my obsessive focus on details helpful.

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