"POLE Mutation" – What Is It?
The POLE mutation describes a genetic change in the POLE gene. POLE mutation carriers have an increased risk of developing multiple colon polyps, colon cancer, endometrial cancer, and possibly other types of cancer. In isolated cases, the POLE mutation is the cause of FILS syndrome and IMAGE syndrome.
How Is "POLE Mutation" Diagnosed?
Experts diagnose using a genetic test for a hereditary change (mutation) in the POLE gene. In the case of an accumulation of POLE-associated tumors within the family, a genetic test for a POLE mutation is recommended. In addition, family members of POLE mutation carriers should also be recommended genetic testing due to the risk of cancer.
Clinical Presentation
Some studies have shown that the POLE mutation is responsible for FILS syndrome. This syndrome manifests in special facial features, immunodeficiency, reddish-bluish skin markings, and short stature.
In addition, according to one study, IMAGE syndrome occurs in isolated POLE mutation carriers and is characterized by prenatal growth retardation, skeletal malformations with shortened limbs, congenital adrenal underdevelopment, and genital anomalies.
What Is the Risk of Cancer?
POLE patients have an increased risk of a variety of different types of cancer:
Colon Cancer
People with POLE mutations have an increased risk of colorectal cancer. The disease called “colorectal cancer-12” is characterized by a predisposition to developing colorectal tumors (adenomas) and malignant tumors (carcinomas). These individuals may present with a few to numerous protrusions of the intestinal mucosa (polyps). The POLE gene is mutated in 5.83% of adenocarcinomas of the colon.
Endometrial and Ovarian Cancer
It is assumed that 7-12% POLE mutation carriers are found among endometrial cancer patients.
According to study results, it is also assumed that the POLE mutation is the cause of a specific subtype of ovarian cancer (endometrioid adenocarcinoma of the ovary).
Non-Small Cell Lung Cancer (NSCLC)
The POLE mutation is also responsible for a non-small cell lung cancer subtype.
Other cancers that probably belong to the POLE spectrum but require further research:
- Malignant solid tumor
- Tumor of the urinary tract
- Skin cancer (basal cell carcinoma)
- Salivary gland cancer
- Squamous cell carcinoma of the penis
- Bladder carcinoma
- Head and neck cancer
- Gastric carcinoma
- Non-Hodgkin’s lymphoma
- Non-clear cell renal cell carcinoma
- Serous adenocarcinoma of the endometrium
- Diffuse large B-cell lymphoma
- Lymphoma
- Mature T-cell and NK-cell non-Hodgkin lymphoma
- Fallopian tube cancer
- B-cell non-Hodgkin lymphoma
- Mantle cell lymphoma
What Is Known About the Development of "POLE Mutation" ?
The POLE mutation is caused by a hereditary change in the POLE gene, which is responsible for a protein that acts as a replicator of our genetic material and prevents uncontrolled cell growth. A mutation, such as the POLE mutation, causes this function to be lost, resulting in uncontrolled cell growth, i.e., a tumor.
POLE mutations are inherited in an “autosomal dominant” manner, which means that parents who are mutation carriers run the risk of every second child developing the disease.
Is There Any Form of Treatment Available?
Patients with the POLE mutation should be treated by an interdisciplinary, multi-professional team. In principle, cancers in POLE mutation carriers are treated similarly to those in non-mutation carriers.
Studies show that the presence of the POLE mutation appears to result in a better prognosis and could, therefore, directly influence treatment decisions. Immunotherapies are currently being researched for POLE mutation-associated cancers, and they appear to be very successful.
The early detection examinations listed below by experts are critical in order to detect tumors in good time and treat them successfully.
Diagnosis of " POLE Mutation" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " POLE Mutation" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Further research is needed into the different manifestations of POLE mutation carriers to develop standardized surveillance recommendations. However, the following screening recommendations are based on the HNPCC recommendations:
- Colonoscopy every 1-2 years: for the first time at the age of 15, then annually from the age of 20 if the findings are normal
- Annual ultrasound examination of the abdomen
- Annual physical examination
- Gastroscopy every 3 years, starting at the age of 20 to 25. If adenomas are detected, at least annual check-ups
- For women: Endometrial cancer screening (transvaginal ultrasound and endometrial biopsy) from 35-40 years of age for POLD1 carriers
As the clinical picture has only recently become known and has therefore not yet been conclusively researched, these are provisional recommendations that may change in the coming years.
POLE Mutation- What You Can Do Yourself
You Should Pay Attention to This
People with POLE mutations should:
- Avoid known carcinogens, including tobacco use, occupational exposure, and excessive alcohol consumption.
- Minimize exposure to diagnostic and therapeutic radiation.
Please contact your treating physician and arrange a prompt appointment in the event of new symptoms, especially blood in the stool, new pain, and parental uncertainty in the assessment of a clinical change. The threshold for making contact should be as low as possible!
Further Information
Unfortunately, we lack any support groups for patients with the POLE mutation. As soon as we have new information, we will add it here.
Any further questions?
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