How do you know if your cancer has genetic mutations?

Hello sheridanb,
Prior to surgery my surgeon ordered genetic testing through a blood sample, but nothing was found. After my surgery I was referred to an oncologist and she ordered a DNA sampling of my tumor tissue and that’s where they found the mutations. My dad had pancreatic cancer and his mother had breast cancer. I was found to have the KRAS12D mutation, TSP or TCP53 mutation and ATM mutation with one of bases a variant of unknown significance which in my mind translates to ATM mutation and not enough research done on that particular base; but still a mutation for pancreatic cancer. My drs early on kept repeating g to me “know your path”! It’s because particular mutations will drive the response to your treatments. A lot of research has been done with the BRCA genes and seem to respond well to treatments. You can also get this information from a biopsy sample. Please talk to your oncologist about this or you can contact PANCAN. There are others on this site who can give you more in-depth response, so I hope you get some more responses.

From my understanding, testing can be done to look for genetic/inherited mutations via blood test, and also on the tumor itself. "Know your tumor" is a program through PanCan that uses tumor tissue from biopsy or surgery to identify biomarkers for targeted therapy. You can ask your Oncologist about blood test and tumor testing.

Tumors mutate, so ideally you want to test a sample from your tumor to learn how to fight it best. As obviously useful as this is, I had trouble getting my oncologists to request this or convincing my insurance to pay for it or something along those lines: I am getting excellent chemo from them, but I actually got this particular testing through a charitable program I found at “pancan.org”.

It could potentially even make sense to get a second sample from your tumor later on if it stops responding to treatment, so your doctors can check for additional mutations that occurred while you were already being treated. (I’m new to all of this, so I have no idea if that is common.)

Testing your blood rather than the tumor gives different information, your body’s baseline mutations. That could tell you that there are particular cancers you might be susceptible to in the future; this can be very useful information for your family, and is still useful information for yourself since life is not fair and you might still have to worry about getting new cancer(s) just like people who were not already diagnosed.

Pdacbrca2, you present a lot of information that I’m familiar with. I never realized cells can mutate into additional new mutations while undergoing treatment. My current pancreatic oncologist did tell me there are 3 mutations for pancreatic cancer; though they can differ among those 3. I do have 3, none of which is BRCA. Thank you for this new information, is this information you gained through your oncologist, research, or maybe a combo of the two?

There are a number of mutations associated with pancreatic cancer, both germline (inherited) and somatic (spontaneous/sporadic) which can be the result of environmental exposure and lifestyle.

These include certain germline mutations linked to driving pancreatic cancer on the following genes:
* BRCA1 and BRCA2
* MLH1, SH2, SH6, PMS2, and EPCAM
* STK11
* ATM
* PALB2
*CDKN2A

The above mutations can also occur as somatic mutations. Mutations found by Next Generation Sequencing (NGS) are:

KRAS mutation-these are the most frequently occurring mutations with the variants G12D, G12V and G12R. The KRAS mutations that are rare but associated with pancreatic cancer in much smaller percentages are G12C (very common in lung cancer) and G12Q61. KRASwt is also a less frequent one but has a better prognosis. KRAS mutations recently became targetable with specific small drug molecules.

Tumors are heterogeneous meaning they are composed of many mutations. Malignant cells are constantly mutating as cancer cells are more prone to breakage and the DNA gets rearranged. Most of the mutations are “fatal” meaning the new arrangement of the DNA makes the cell unsurvivable. When a non-fatal mutation occurs, That cell proliferates. The mutation can confer drug resistance. Tumors are not perfectly spherical. This is because a mutation can result in faster or slower growth in the area of the tumor it occurs.

When you see a tumor where a side might be elongated while undergoing chemotherapy or the liver metastasis are shrinking but the primary tumor is not, it indicates different mutations occurred in the primary giving it resistance. The primary tumor and the metastatic tumors all contain different mutations in addition to having many in common. This is why multi-drug chemo agents are more effective than single drugs.

For family members to determine genetic risk factors, a liquid biopsy on blood or saliva is performed. This would be done on family members directly related. Insurance covers the testing when it is a direct blood relation such as one’s mother, father, sister or brother. Sometimes they will pay if a parent or sibling that had cancer is deceased. My testing was covered despite my mother and grandmother, great-aunt, a first-cousin once removed and a first-cousin twice removed having breast cancer.

For somatic testing of the tumor, PanCan.org offers a free testing program called “Know Your Tumor”. The program was set up by the Skip Viraugh Foundation covering the cost of the analysis by Tempus Laboratories located in Chicago. More information is at the following link and a case manager at PanCAN.org will provide information and printed instructions on how the pathology department is to submit the sample.

@stageivsurvivor, @marienewland, @pdacbrca2, @ashley2235, @marienewland
Thank you all for your responses! We will talk to our oncologist about this. I did find, from a blood test last summer I think, that krasg12r, tp53, and smad4 were mentioned with "no msi high" . We'll see if there is any tissue from biopsies available for further testing.
So much to learn, and I find it so confusing. But are grateful for you taking the time to respond.

i had extensive genetic testing in the Genetics dept of the University of Miami a few years ago. That is how i found out about my gene mutation

You mention that KRAS is now targeted with specific small drug molecules. Please name what these drug or drug combinations are and if primarily for KRAS g12c? I have not uncovered anything for kras g12d. Thank you!!

Yes so much to learn, but so many on this board to help each other!

@stageivsurvivor, thank you so much for the wealth of information you provided! I was not aware that mutations mutate; no wonder it’s so difficult to fight pancreatic cancers. That explains why my liver lesions responded well to my GAC treatments, yet the abdominal masses are still just stable. Unfortunately, my dr was not able to get a tissue sample of those abdominal masses or the hepatic artery soft tissue. And then there are proteins (like CLD18.2)within the membranes of cancer cells which feed these cells to keep them active. So much more research is needed for us ATM and KRAS12 types. Gold bless all the researchers out there!