Understanding POLE testing and Its Implications


Genes play a crucial role in how we understand diseases like cancer in today's medicine. The POLE gene is an important gene linked to certain cancers. GOPATH offers germline POLE sequencing under our Comprehensive 88 Gene Panel and somatic sequencing of POLE as a single-gene test for Endometrial cancer, or as part of our FDA cleared genomic profiling panel- ONCOTarget500 for advanced solid tumors. This article will explore the POLE gene, its importance, potential risks, and its connection to endometrial cancer.

The POLE Gene: A Brief Overview

The POLE gene helps protect against cancer. Mutations or changes in this gene can increase the risk of developing certain cancers. However, just having a mutation doesn't mean you will get cancer, it just raises the chance. While this gene can affect anyone, changes in it are often linked to endometrial cancer, a type of cancer that starts in the lining of the uterus.

Polymerase Proofreading-Associated Polyposis Syndrome (PPAP)

Certain changes in the POLE gene caused by inherited(germline) mutations can lead to a condition called PPAP syndrome. This condition means you're more likely to have growths, called polyps, in your colon and rectum, which can increase the chance of developing colorectal cancer. Women with this condition might also have a higher chance of getting uterine cancer, though research is ongoing in this area.

Endometrial Cancer

Endometrial cancer is the most common cancer found in women's reproductive organs in the US. It has different types, and genes can affect which type a person might get. Two important genes are PTEN and TP53.

PTEN Gene: This gene acts as a regulator of cell growth. A dysfunctional PTEN gene can result in uncontrolled cell proliferation, leading to certain forms of endometrial cancer.

TP53 Gene: Dubbed the guardian of our DNA, the TP53 gene ensures cells with flawed DNA neither grow nor survive. In the context of endometrial cancer, TP53 malfunctions can lead to more aggressive cancer forms.

The POLE-Endometrial Cancer Connection

Endometrial cancer can exhibit a connection to genetic variations in the POLE gene. Certain instances of endometrial cancer harbor mutations in the POLE gene, which distinguish them from other cases. Interestingly, these cancers with POLE mutations often display an increased number of DNA alterations. Paradoxically, such cancers tend to respond more favorably to treatment, leading to improved outcomes.

Medical professionals find this development promising because it suggests that these cancers may be receptive to a specialized form of therapy known as immunotherapy. Immunotherapy assists the body's immune system in targeting and combatting cancer. In essence, the presence of POLE gene mutations can influence the behavior of endometrial cancer and, subsequently, the available treatment options.

POLE Mutation and Family Risk

If you have a germline POLE mutation, there's a 50% chance that your biological parents, siblings, and children may also carry the same mutation. Even your more distant relatives could potentially be at risk.

It doesn't matter whether you're male or female; both genders have an equal chance of passing down this mutation in the family. Just inheriting it from one parent can increase your risk of cancer. Your genetic counselor will assess your family history and discuss whether genetic testing for your blood relatives is recommended. The counselor will offer insights into the specific cancers linked to the mutation and recommend appropriate screening measures.


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