At the Intersection of CDH1 Mutation and Genetic Testing
Hanne Livermore
University of Illinois at Urbana-Champaign ‘25
Premedical Molecular and Cellular Biology Student
As we know, Justin was diagnosed with stage IV stomach cancer, also known as gastric cancer. The disease can be just as daunting mentally, as it is physically. This piece minimizes the initial choked-up feeling we get when we hear the word ‘cancer’ by explaining how it works at a cellular level; with knowledge comes power. I write this to bridge the gap between an everyday audience and a complex disease usually explained with unfamiliar medical terms. Everyone deserves to have the choice to understand their body.
To begin, we can break down what the disease looks like from a molecular perspective. The cells in your body contain all of the genetic materials that make you, you. We call this your DNA. This DNA undergoes a series of transformative processes science has named ‘the central dogma’ of biology. In short, the DNA is replicated, transcribed into RNA (genetic material similar to DNA, but with a slightly different chemical makeup), and finally translated into proteins. These protein products are what allow our bodies to function properly. If your body does it, it's thanks to protein. Errors, also called mutations, can occur in the DNA. These mutations can lead to changes in the corresponding protein function.
Our bodies acquire millions of mutations throughout our life, most of which have no effect on our health. Although in some rare and unfortunate cases, these mutations can have a severe effect. These errors in your DNA can be acquired through exposure to carcinogens or may be inherited, like in Justin’s case. Only about 2% of diffuse stomach cancer cases are hereditary. This inherited mutation is on the 16th chromosome, in the CDH1 gene. This mutation does not automatically mean you have cancer, but it does mean that you are more likely to develop cancer. If one does end up being diagnosed, there are a multitude of treatment options to treat or even eliminate the disease.
The CDH1 gene encodes for a protein called E-cadherin. The protein is responsible for connecting epithelial cells; the cells that coat the innermost and outermost surfaces of the majority of your body’s tissues. Think of the epithelial cells as tiles, and the E-cadherin as the grout between the tiles. These proteins work to connect the cells and uphold their collaborative structure.
Cancer has been a prominent cause of fatalities and emotional stress for thousands of years, but our understanding of it at a cellular level has advanced only in the last fifty years or so. So you may ask, what actually is a tumor? A standard tumor is an unnatural mass of cells. Most cells in your body are not multiplying. Your body is aware of when it needs to create new cells, and when it does not. This is dependent on a basic schedule as well as environmental stimuli. Certain mutations can lead to uncontrollable cell multiplication, which we term cancer. A mass of such cells is a tumor. The CDH1 gene that encodes E-cadherin is a “tumor suppressor gene.” One of the primary signals that tells cells to NOT replicate is the connection between them. The absence of E-cadherin can lead to uncontrolled epithelial cell growth.
In the case of diffuse gastric cancer, there isn’t a solid mass of cancerous cells that can be targeted and removed. Instead, small clumps of cancer cells aggregate in a dispersed manner throughout the inner lining of the stomach. Instead of being in one singular location, they are evenly spread throughout the tissue in much smaller quantities. Again, they are not being held together by E-cadherin. This becomes hazardous as the cells continue to multiply exponentially. The volume and structure of our anatomy cannot handle the sheer amount of cells. There is such an abundance that the stomach begins to become dense and very thick. Science has named the symptom 'linitis plastica’, Latin for ‘leather bottle’. This overgrowth and stiffening of the tissue then continues to spread to the outermost lining of the stomach and can affect surrounding tissues such as your liver. When these tissues become stiff, they gradually lose their flexibility, interfering with their normal functions: In the case of the stomach, breaking down the food we eat into absorbable nutrients. As you can see, this minute error in your DNA can make a huge difference in tissue function and your health.
The good news is that it is possible to find DNA mutations, thanks to genetic testing. Scientists have developed amazing strategies to examine your genetics in order to keep you in the know of what your body may have in store for you and how you can be better prepared for it. By choosing to participate in genetic testing, you can take a closer look at single genes and what kinds of changes or mutations you may possess, or even examine your entire genome for an overall analysis. The activity of certain proteins can even be measured, telling you how well they are doing their job. There is an immense variety of genetic testing available. What may seem like something far too complex for your own understanding can be made much simpler by professionals. They can help create an individualized plan for you and your family to ensure you are taking precautions and living a lifestyle best suited for you. Understanding your genetics can make a lifetime of difference.
Sources
Information on this page was compiled from a number of independent sources and is not owned by HardyStrong Foundation.
Acknowledgements
James M. Slauch
Professor and Head of Microbiology and Director of Medical Scholars Program at the University of Illinois at Urbana-Champaign
B.S. (Biochemistry), The Pennsylvania State University, 1984
Ph.D. (Molecular Biology), Princeton University, 1990
Postdoc. (Microbiology), Harvard Medical School, 1990-1993
Anna Marie Sokac
Associate Professor of Cell and Developmental Biology at the University of Illinois at Urbana-Champaign
B.S. (Biological Sciences), Carnegie Mellon University, 1990
Ph.D. (Cell and Molecular Biology), University of Wisconsin-Madison, 1994
The Central Dogma (Source)