Hereditary Cancer Risk vs. Somatic Mutations: What Questions Does an NGS Tumor Profile Answer?

When patients and their families receive a cancer diagnosis, the first question that usually comes to mind is: "Is this disease genetic? Will it be passed on to my children or siblings?"

Cancer is, at its core, a genetic disease. This is because cancer cells are cells that multiply uncontrollably due to coding errors (mutations) in their DNA. However, the concept of a "genetic disease" does not always mean an "inherited disease passed down from the family." In the world of oncology, these genetic errors that lead to cancer are divided into two main categories: Somatic mutations and Hereditary (Germline) mutations.

Knowing the difference between these two concepts is of vital importance when planning treatments for cancer patients and calculating the cancer risk for healthy individuals. In this guide prepared by the Oncogencell Comprehensive Genetic Profiling Center, we examine in detail what somatic and hereditary mutations mean, the critical differences between them, and what questions the advanced NGS (Next-Generation Sequencing) Tumor Profiling test answers within this complex structure.

Cancer and Genetics: Understanding the Basic Concepts

In the nucleus of every cell in our body, there is a manual that determines how that cell will grow, how it will function, and when it will die. We call this manual DNA. The meaningful code segments within the DNA are called genes. If a typographical error (mutation) occurs in these genes, the cell's manual becomes corrupted. The cell forgets when it is supposed to stop and starts dividing continuously, eventually forming a tumor (cancer) mass.

When and how these "typographical errors" enter our bodies determines whether the disease is somatic or hereditary.

What is a Somatic Mutation? (Acquired Errors)

Approximately 85% to 90% of all cancer cases develop as a result of somatic mutations. "Somatic" means relating to the body. Somatic mutations are not genetic errors that a person inherits from their mother or father. They emerge later in life, entirely due to the effects of environmental factors or biological aging.

What are the Causes of Somatic Mutations?

Our cells renew themselves by dividing throughout our lives. Sometimes, during this division, the DNA makes completely random "copying errors" while replicating itself. Apart from this, there are external factors that damage the DNA of our cells and trigger these errors:

• Use of tobacco and tobacco products,

• Radiation received from the sun (UV) or devices,

• Exposure to toxic industrial chemicals,

• Poor diet, obesity, and advanced age.

Characteristics of Somatic Mutations

The most fundamental characteristic of somatic mutations is that they are found only in the cancerous tissue (the tumor). For example, if a somatic mutation occurred in your lung due to environmental factors, we can only find this mutation in the tumor cells in your lung; it is not in your blood, saliva, or healthy skin cells. Most importantly, because somatic mutations are not present in reproductive cells (sperm or egg), they cannot be passed on to your children (they are not hereditary).

What is a Hereditary (Germline) Mutation? (Inherited Risk)

About 10% to 15% of all cancers occur due to hereditary (germline) mutations. These mutations are present when the person is just a single cell in the mother's womb (through the fusion of sperm and egg). The person has directly inherited this corrupted genetic code from their mother or father.

Characteristics of Hereditary Mutations

• Because they are acquired through inheritance, they are present in every single cell in the body (blood, hair, skin, saliva, etc.) from birth.

• Individuals carrying this mutation are born "one step closer" to cancer risk. In other words, the cells in their bodies are much more prone to becoming cancerous.

• The most well-known examples are BRCA1 and BRCA2 gene mutations, which significantly increase the risk of breast and ovarian cancer, and Lynch Syndrome mutations, which increase the risk of colon cancer.

• Because hereditary mutations are also present in reproductive cells, there is generally a 50% chance of passing this gene on to the children of individuals carrying it.

Somatic vs. Hereditary Cancer: What Are the Key Differences?

To summarize these two concepts more clearly for patients and their relatives, we can speak of 3 fundamental differences:

1. Starting Point (Timing): You are born with a hereditary mutation (it exists at the 0th second of life). You acquire somatic mutations while living, over the years, due to environmental factors or by chance.

2. Location in the Body: A hereditary mutation is present in all your healthy/unhealthy body cells (it can be tested from blood). A somatic mutation is found only inside the cancerous tumor.

3. Transmission to the Family: A hereditary mutation can pass to your children and poses a risk to other family members (siblings, cousins). A somatic mutation only concerns the patient themselves and does not pass to children.

What Mutations Does the NGS Tumor Profiling Test Detect?

When starting cancer treatment, medical oncologists want to know which genetic errors (mutations) are present in the patient's tumor. Because if they know these errors, they can use smart drugs (targeted therapies) that directly target that specific error.

The Next-Generation Sequencing (NGS) Tumor Profiling Test (OCA Plus) that we apply in Oncogencell laboratories is performed on the tumor tissue (biopsy material) taken from the patient. The primary purpose of this test is to find the Somatic mutations that have formed subsequently within the tumor. Our devices, which scan 517 genes simultaneously, report the weak points of the tumor, which smart drug will work, and whether the patient is suitable for immunotherapy (TMB, MSI, HRD levels) with millimeter precision.

Can Hereditary Cancer Risk be Discovered by Taking a Tumor Test?

This is the question our patients ask most frequently and causes the most confusion: "Since you are analyzing the tumor with NGS, can you also tell from this test whether my cancer is genetic (familial)?"

The answer is both yes and no. In medical literature, a Somatic Tumor Test does not directly replace a hereditary (germline) cancer risk analysis. This is because tumor tissue is like a "soup" that simultaneously harbors both hereditary mutations (if present, they are in the tumor just as they are in all cells) and subsequently acquired somatic mutations. When we see a BRCA mutation in the NGS result from the tumor, we cannot distinguish with 100% certainty in the laboratory whether this was "inherited from the family" or "only formed subsequently in the lung." The only way to know the hereditary risk clearly is to conduct a separate analysis (Germline Test) from healthy cells, i.e., from blood or saliva.

What Happens if a Secondary Finding is Detected? The Oncogencell Approach

During the comprehensive genetic testing we perform on the tumor, although our primary goal is to find smart drugs, we may encounter some mutations in the tumor tissue (e.g., BRCA, PALB2, TP53 mutations) that we suspect might be familial. In medicine, this is called a "Secondary Finding."

Encountering a secondary finding is a very critical turning point for the patient and their family. As Oncogencell, in line with our ethical and holistic health vision, we never ignore this situation. In such a scenario, our process works as follows:

1. Free Genetic Counseling: If a possible hereditary finding is detected in our somatic panel, the Medical Genetics Specialist physician within Oncogencell contacts our patient and their doctor. Comprehensive and entirely free genetic counseling is provided to our patient regarding the process.

2. Referral for Blood Confirmation Test: To verify whether the suspicious gene found in the tumor is truly hereditary (i.e., whether it carries the risk of passing to children), our patient is referred for specific germline (hereditary) genetic tests performed on blood.

3. Protecting Family Members: If it is confirmed in the blood test that the mutation is hereditary, the patient's healthy siblings and children can also be screened. If this gene is detected in family members who have not yet developed cancer, the lives of healthy individuals are saved through preventive surgeries or very strict screening programs (early diagnosis).

Conclusion: Why is it Important to Read Your Genetic Code Correctly?

Understanding the genetic basis of cancer is like turning on a flashlight in a dark tunnel. Knowing whether the source of the disease is somatic or hereditary not only ensures that the most accurate and effective smart drug is selected for you, but it also provides a unique opportunity to protect the health of your future generations, children, and siblings.

There is no room for assumptions in modern oncology. Comprehensive analysis is essential to plan your treatment in the most accurate way and to reach scientific facts about your genetic heritage.

You can contact Oncogencell immediately to profile the molecular structure of your tumor, get information about our NGS testing processes, and request genetic counseling from our expert physicians.

Disclaimer: The medical information in this article is prepared to inform patients and their families about genetic tests. It does not replace a physician's examination, medical diagnosis, or direct treatment recommendation. The evaluation of the hereditary and somatic characteristics of cancer should be carried out with the decisions taken by a multidisciplinary council of medical genetics specialists and medical oncologists.