Combining Germline and Somatic Cancer Testing for better Cancer Treatment

Dr. Rohit Raghunath Ranade, MS, MCh

Consultant, Gynae Oncology & Robotic Surgery
Mazumdar Shaw Medical Center, Narayana Multispeciality Clinic, Narayana Multispeciality Hospital, Bangalore

In this blog, we will read, in detail, about how combining germline & somatic testing for cancer treatment can be better as cancer can be a multifactorial disease at times.

Cancer is a heterogenous disease of our genome where our DNA gets altered/mutated from normal sequence due to internal or external influences. On the other hand, cancer can also be termed as ‘Multifactorial Disease’ too. 

Altered DNA sequence will encode abnormal proteins which is lethal for a normal cell in respect to growth, proliferation, division and apoptosis. These changes in DNA sequence are termed as Genetic Mutation or Genomic Alteration. Once this mutation/alteration is occurred the normal cells fail to behave as normal cells and transformed to a cancerous cell.

This genetic mutation or genomic alteration can be of many types but according to the cell of origin it is of two types of Germline and Somatic.

Germline mutation are those types of mutation or alteration which are occurred in our germ cells or the mutation with which we are born with and are passed on from generation to generation in each family for a specific disease in this context its cancer. As the germline mutation is present in all the cells of our body so best sample sources are blood or saliva to test them. Whereas Somatic mutations are non-hereditary mutations where a particular individual acquire this mutation in their course of life. This acquisition can be due to poor lifestyle, tobacco consumption, occupational hazards etc. Somatic mutation that causes a cancer is confined to the origin tissue of an individual. For an example, if someone has a habit of smoking, he/she has high chance of somatic mutation causing cancer in lung, throat or oral, the part of the body that are exposed to smoke. So, the sample source of the test is tissue of the cancer/biopsy of that cancer tissue.

Based on evidence it has been seen that frequency of germline mutation in a population is about 5% to 10%, whereas the somatic mutation is quite prevalent in our population and the frequency of somatic mutation in a population is more than 95%. 

So, the screening of both mutations is equally important in clinical practice. If a family has a strong history of breast cancer then the members should screen for those genes that are responsible for breast and associated cancers. By doing this one can reduce the chance of developing cancer with better lifestyle management or by clinical management, even they can undergo risk reduction surgery or treatment.

When an affected individual comes to a clinic the clinician first tries to understand the history of the disease whether its hereditary or not and then to find out the underpinning genetic cause of that cancer, he/she suggests for comprehensive profiling of the whole of patients’ tumor genome by next generation sequencing technique. Even if that particular patient has strong history of cancer running in their family, he/she is advised for germline mutation causing cancer testing too. Once both the reports are with the clinician, he/she can design the treatment plan for that particular patient and also can guide the immediate family members those who have inherited those pathogenic cancer-causing genes with risk reduction procedures.

Based on somatic testing results a clinician can treat the affected individual with FDA approved targeted drugs available and also, he/she will have options for use of Immunotherapy treatment regimen if needed in future. So, the doctor has bucket of options available for precise treatment by minimizing the side effects of non-specific drugs based on the genomic landscape of the disease for that particular individual. 

Sometimes one’s tumor may harbor non-actionable somatic mutation, means that for these mutations no specific drugs have been approved/available. In that case, doctor can counsel the patient to enroll in Clinical Trials. 

So, practically there is lots of scope for genetic testing, by germline you are informed about the mutation status that runs in your family (If you have strong family history of cancer) for a hereditary cancer and by somatic testing you are getting personalized treatment option with minimal side effects by analyzing the DNA/RNA variants of the tumor genome

So, it is clearly evident that if a particular cancer patient has strong family history of cancer then along with somatic mutation testing, he/she should also go for germline testing to know the status of the cancer causing pathogenic mutation running in his/her immediate family member for their risk reduction procedure which will in turn help them to counter the disease well in advance.

So, there is clear need of doing both germline and somatic mutation test for better management of the individual patient treatment and also to minimize the risk of developing cancer for his/her immediate family member well in advance.