We usually denote the origin of a mutation as either somatic or germline. This information is usually available in certain databases such as CIVIC, ClinVar, COSMIC etc. But when we come to variants that have been denoted as "Overexpression", "Upregulation" , "Methylation" etc., what would be the origin? Any leads would be very helpful. Thanks in advance.

For example from Cristina Aguirre‐Portolés et al., 2018:

ABCA1 is significantly overexpressed in patients at advanced stages of colorectal cancer, and its overexpression confers proliferative advantages together with caveolin‐1 dependent‐increased migratory and invasive capacities. Overexpression of ABCA1 was associated with overall survival independently of the molecular subtype of the cancer.

Does this overexpression phenomenon arise in the germline or does it happen somatically? How do we conclude?

  • $\begingroup$ I don't really think you can if it wasn't mentioned in the paper... $\endgroup$
    – terdon
    May 28 '19 at 9:41
  • $\begingroup$ @terdon Does it make sense that when we say "Overexpression", we refer to expression of a gene using normal expression as control? As in, when we measure the expression level we also take a normal from healthy tissue. So doesn't it mean that this overexpression is in fact a somatic event? $\endgroup$ May 28 '19 at 11:34
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    $\begingroup$ There is no one answer to that. It will always depend on the specific context. The control could be normal tissue vs tumor, yes, but it could also be healthy individuals vs patients. Or 10 days after diagnosis vs. 2 years after diagnosis. In the example you cite, we cannot know if the overexpression of ABCA1 is limited to the tumor cells or systemic in the entire body. Perhaps there is an immune response to the tumor that stimulates systemic overexpression. There could be any number of possibilities. $\endgroup$
    – terdon
    May 28 '19 at 11:40
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    $\begingroup$ Actually, it does seem likely that they are referring to the tumor since they mention increased migratory and invasive capacities and Overexpression [...] was associated with overall survival independently of the molecular subtype of the cancer, but it isn't clear from your extract what they are comparing to. In any case, there will not be one single answer here and it will always depend on the specific study. $\endgroup$
    – terdon
    May 28 '19 at 11:43
  • $\begingroup$ @terdon Ok that makes it a lot clearer now. Thank you for your help ! $\endgroup$ May 28 '19 at 12:01

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