NRAS Mutation

Posted By
Anonymous
7/31/2014 8:10pm
Activity
Replies: 11

I just learned that my wild type melanoma tumor has the NRAS mutation.  I have had one recurrence since initial diagnosis that was surgically removed.  I am stage III after the last tumor removal.  

What are some of the potential treatments for this tumor mutation?

Thanks.

sweetaugust - (8/1/2014 - 10:57am)

I too, am wondering about this NRAS mutation.  I have been stage 4 and have been on the Merck pd1 MK-3475 for two years so far, and there is no end date for my drug infusions.  I'm doing great and really have no complaints and feel very lucky and blessed to be feeling fine and living a totally normal life at 40 years old. 

I didn't really do any research into any of this melanoma stuff until this winter, when I became curious as to why my side effects of treatment seem to act up more in the winter months than in the summer.  And that is when I found this site. 

People are always talking about BRAF and I never looked up what that really means, but I kept meaning to ask my doctor each time I went if I were BRAF positive or negative.  I finally asked this week and they said I am the wild type with the NRAS mutation.  They said it's very rare and only 10% of the melanoma patients have that mutation and that they are working on trials to help it.  I left the office before I even thought any further about it.  But yes, I too am now wondering more about this NRAS mutation.

I don't know if that helps you to know that I too have this NRAS mutation as well and I am on the MK-3475 drug trial and am doing great.  Stable and no longer progressive disease since this past Christmas.

Best of luck to you,

Laurie

Anonymous - (8/1/2014 - 8:47pm)

It does help to hear that others are feeling great while living with advanced melanoma .

Did you start MK-3475 after becoming Stage 4?  

sweetaugust - (8/4/2014 - 9:42am)

Yes, I found out I was stage 4 on Oct 1, 2012 and I started MK-3475 on Oct 31, 2012.  Most of my mets responded right away and disappeared.  One met was more aggressive and kept growing for a few months before it responded.  It made it to the size of a baseball, and it has now shrunk to the size of my thumbnail. 

RJoeyB - (8/1/2014 - 11:37am)

I had a "genetic testing" conversation with my medical oncologist about a year ago (he's the co-director of my cancer center's melanoma program and also an advisor to their genomic institute) about BRAF, CKIT, NRAS, etc. and the value of any broader genetic tests with melanoma.  At the time, I brought it up primarily in the context of BRAF, since I'm BRAF positive, but was curious about other mutations, too.  Again, this conversation was a year ago so please use this information just as a starting point...

Roughly 50% of melanoma patients are BRAF positive.  You can read more about what that really means with regards to genetic specifics in other posts - Celeste who posts here regulaly has some terrific explanations on her blog.  They think perhaps only 10-15% of melanoma patients have the NRAS mutation.  Interestingly, the BRAF and NRAS mutations seem to be almost mutually exclusive; in other words, it's very rare to find someone with both.

There seemed to be more discussion about targeting NRAS in 2013 than I've heard this year, specifically about trials using a drug called MEK162, which is an MEK inhibitor being developed by Array BioPharma.  I think Novartis has partnered with them on it, too.  If you Google "MEK162 melanoma" you should find lots of information.  I just found this on Array's site and it might be a good place to start (it looks like MEK162 has a name now, too (binimetinib):

http://www.arraybiopharma.com/product-pipeline/binimetinib/

Hopefully this helps you get started,

Joe

Anonymous - (8/1/2014 - 8:49pm)

Thanks for the lead.  I will check out this trial.

Anonymous - (8/1/2014 - 8:58pm)

Thanks for the lead.  I am interested in having a conversation with my doctor  at my next visit.  Now that I know that wild types have variable, I can ask better questions.

kylez - (8/1/2014 - 2:01pm)

I'm not sure that all NRAS mutations are the same. Just read this today, http://www.ncbi.nlm.nih.gov/pubmed/25043451. In particular, "[NRAS mutated...] most frequently at glutamine 61 (Q61: ~86% of cases), but also at glycine 12 (G12; ~8% of cases) and G13 (~4% of cases)." 

Mine is a rarer one, G12A. "Notably, Q61 NRAS mutations are mutually exclusive with V600 BRAF mutations." Does that mean G12s like mine are non mutually exclusive with V600 BRAF? 3 years ago I did not have BRAF mutations. Now 3 years later who knows?

Here's one NRAS-specific clinical trial, http://clinicaltrials.gov/ct2/show/NCT01781572?term=nras%20and%20melanoma.

-Kyle

Anonymous - (8/1/2014 - 8:44pm)

Thanks for the leads in possible treatments.  I am be vigilant about noticing lumps under my skin and have follow up visits at the melanoma center every three months.  Now that the genetic testing is done and I have more information about my specific type of melanoma, I can consider the options available in addition to watch and wait.

JerryfromFauq - (8/4/2014 - 3:12am)

DO YOU HAVE ANY IDEA WHAT A "WILD TYPE TUMOR" IS?  

What gene does the report say is "Wild Type"  (i.e. with no cancer mutation).

:    Here is a question & response that I asked about mutation testing and WILD TYPE genes  and Dr Keith Flahety's response.................................................. ,

I have some general questions that relates to genetics genomics, nomenclature. etc. :

One question there has been debate about is how the Term "Wild Type" is used. By definition it seems this is the most common form of gene and is considered "unmutated" as far as being cancerous after being tested. I have seen the term such as BRAF and c-kit negative used to mean "unmutated". From my reading it appears that neither is quite accurate without a further qualifyier. Do any of the tests actually show nonmutated" or do they just test for specific mutations and say negative for those and then say "WT"? How do the cases of oncoprotein over expressiom and ------mutation Negative fit in? IS this because a known carcinogenic mutation wasn't found, vice saying that there is no mutations in the genes?

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Re: Mutation Testing Question

Postby Keith Flaherty » 26 Aug 2013 12:37
Regarding the question about mutation testing for the mutated oncogenes that we now consider to be the critical ones for which therapies are either validated or in clinical trials, I would put it this way:

Certain melanoma oncogenes, such as BRAF and NRAS, are analyzed using tests that are specifically designed to detect the most common mutations that can occur in those genes that result in a constantly active form of the resulting molecule. These tests come out as either positive or negative. Positive means that the specific mutation being probed was found, negative means that it was not. The gene most certainly exists in its wild type (nonmutated) form in those cases that are reported as negative. CKIT and, on occasion, BRAF and NRAS can be analyzed by "sequencing" in which case the result will not be positive or negative, but rather indicate whether the elements of the gene being sequenced are mutated or nonmutated and, if mutated, where those mutations are found. This is especially important in the case of CKIT since we know that there are several different mutations that can affect the gene and activate the resulting molecule.

 

I'm me, not a statistic. Praying to not be one for years yet.

JerryfromFauq - (8/4/2014 - 3:20am)

Correlation of NRAS Mutations with Clinical Response to High Dose IL-2 in Patients with Advanced Melanoma

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241890/

Overall, 47% of the NRAS-mutant patients achieved a CR/PR, as compared to 23% with a BRAF mutation, and 12% of WT/WT patients. Patients with NRAS mutations had a significantly higher response rate when compared to patients with BRAF mutations or were WT (Table 4) (47% versus 19%, p=0.04)

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IL-2 and PD-1 are the only two treatments that offer a near 50% positive rewponse rate to NRS Melanoma's.

I'm me, not a statistic. Praying to not be one for years yet.

Anonymous - (8/4/2014 - 4:42pm)

At the beginning of my melanoma journey my melanoma mutation understanding was BRAF + or BRAF -.  Other mutations were not part of my understanding until I had a recurrence  and used what I had learned from this board to insist on additional testing. 

Thanks for the additional insight from your doctor.