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.
https://pancan.org/facing-pancreatic-cancer/patient-services/know-your-tumor/