Patched-1, or PTCH1, is a tumor suppressor gene, meaning it helps prevent certain types of cancers from developing. When you have a PTCH1 mutation, the gene’s cancer-suppressing effect no longer works. A PTCH1 mutation is associated with Gorlin syndrome, a hereditary disorder that can increase your risk of noncancerous and cancerous tumors, including basal cell skin cancers, as well as certain developmental and skeletal abnormalities. Mutations can also lead to other types of cancer, including nonhereditary types of basal cell cancers, breast cancer, colon cancer, and medulloblastoma, a type of brain cancer.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293a3eb882-6c98-4fc1-ae1e-6d8a97437351
What Is the PTCH1 Gene? What Is It? Everyone inherits two copies of the PTCH1 gene from their parents.e60dc2a1-f33c-4a05-9b50-8e3e8e597629af04ece3-76aa-4ca8-8c5a-8c52d4a690f7 The PTCH1 gene provides your body with instructions to make patched-1 protein, a type of receptor protein. These proteins bind to another type of protein (ligands), known as Sonic Hedgehog ligands. Together, PTCH proteins and Sonic Hedgehog ligands work as a pathway, referred to as a hedgehog pathway, triggering signals that lead to cell growth and development.e60dc2a1-f33c-4a05-9b50-8e3e8e59762917fef898-ee5a-4968-9405-9d9029753940 Mutations in the PTCH1 gene can cause these signaling proteins to not work properly. Issues with the hedgehog signaling pathway are associated with developmental abnormalities and cancer, including Gorlin syndrome and nonhereditary types of cancer.e60dc2a1-f33c-4a05-9b50-8e3e8e5976299dc9b28e-4e35-4acc-8a5e-2b5b98c37906 In fact, people with Gorlin syndrome, which is one abnormality caused by a PTCH1 mutation, may develop basal cell carcinoma in infancy, though the median age is 20 years old.e60dc2a1-f33c-4a05-9b50-8e3e8e597629fe4b2207-780f-452d-95c5-8de2235f190c “There are over 100 clinical abnormalities that can happen,” says Joe Mignone, MD , oncologist and cofounder of SurvivorRx. They’re “usually diagnosed at a young age, but they may not be detected in some until their teens or young adulthood.”
Causes and Risk Factors for PTCH1 Mutations Causes and Risk Factors “A PTCH1 mutation is rare, estimated to be between 1 in 31,000 to 1 in 164,000,” says Dr. Mignone. “True numbers may be higher, as some people with mild features and symptoms may never be diagnosed.” Most people with a PTCH1 mutation will inherit the PTCH1 gene variant from their parents, but it is still possible to spontaneously develop the mutation later in life. Mignone says that 70 to 80 percent of the risk factors and causes are inherited, with 20 to 30 percent occurring spontaneously, or de novo. People only need to inherit the gene mutation from one parent in order to have an increased risk of developing cancer.e60dc2a1-f33c-4a05-9b50-8e3e8e59762927c9701f-3310-4bb8-929f-2fbe358c2306
Risks and Complications of PTCH1 Mutations Risks and Complications “PTCH1 gene is a tumor suppressor gene generally associated with Gorlin syndrome,” says Mignone. In fact, PTCH1 mutations are responsible for about 50 to 85 percent of Gorlin syndrome cases, with over 225 mutations of the PTCH1 contributing to the condition.e60dc2a1-f33c-4a05-9b50-8e3e8e59762965bb8e48-2873-4a2c-bb5e-3a51ee13f993e60dc2a1-f33c-4a05-9b50-8e3e8e597629cb2dd9db-6e49-4e69-8705-16bacacddfc5 Gorlin syndrome is rare, affecting 40,000 to 60,000 individuals. It affects men and women equally and is present in all races, though African American and Asian individuals may have a lower risk of the condition, making up 5 percent of all cases. Gorlin syndrome can lead to the development of both noncancerous and cancerous tumors and developmental abnormalities, including: Keratocystic odontogenic tumors, or noncancerous (benign) tumors of the jaw Medulloblastoma, a type of cancerous, fast-growing brain tumor that develops in the cerebellum e60dc2a1-f33c-4a05-9b50-8e3e8e597629b5690f6b-98d4-4c46-83d2-5dc3bb95e47a Cardiac or ovarian fibromas, which are typically benign tumorse60dc2a1-f33c-4a05-9b50-8e3e8e597629d5b790b2-c320-4d6a-b092-6aaf18297afc Superficial pits in the palms and soles of the feet, which around 75 to 90 percent of people with Gorlin syndrome havee60dc2a1-f33c-4a05-9b50-8e3e8e597629e2e3832d-b1fe-4a88-ba4c-91a9faff5273 Macrocephaly, or a very large heade60dc2a1-f33c-4a05-9b50-8e3e8e597629cb2dd9db-6e49-4e69-8705-16bacacddfc5 In addition, “Those with PTCH1 mutations can have bone and eye problems,” says Mignone. “The mutation is also associated with cleft lip or palate, and those with the mutation may be born with extra fingers or toes.” While experts know that PTCH1 mutations can cause an increased risk of certain cancers, they are not as certain how the mutation relates to other changes associated with Gorlin syndrome.
Testing for PTCH1 Mutations Testing “PTCH1 genetic testing typically uses saliva or blood, and someone should be tested whenever they have any features or family history of Gorlin syndrome,” says Mignone. Kenneth Mark, MD , a cosmetic dermatology expert in New York City, also recommends that people with a family history of a PTCH1 mutation undergo testing for it. If you’re looking to start a family, you may want to undergo prenatal testing if you or your partner has a PTCH1 mutation. “If a parent has the gene, then there is a 50 percent chance of the fetus acquiring it as well,” says Mignone. It is always advised to meet with a genetic counselor so that proper testing is performed.” If you or your partner has the mutation, you can discuss potential options to reduce the risk of passing it on with a genetic counselor.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295d6e64f0-9e63-4991-a615-34c6870bf85a
What Are Your Next Steps if You Have a PTCH1 Mutation? Next Steps If you test positive for a PTCH1 mutation, your doctor will review your medical history, including your personal and family cancer history. They may recommend getting cancer screenings more frequently or that you start screenings at a younger age.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292a0ce1cc-4731-44a4-9260-968c39e3b35a Having a risk factor for cancer does not mean you will develop cancer. It just means you have a higher risk compared with someone who doesn’t have the mutation. If testing confirms you have a PTCH1 mutation: Contact your doctor to discuss your results and their recommended next steps. Schedule a meeting with a genetic counselor if you’re planning on getting pregnant. Discuss screening schedules for skin cancers, as well as any other cancers you have a family history of, with your doctor. Take extra precautions to protect your skin, such as wearing sunscreen, staying in shade, and wearing large hats when you’re outside.
Are Treatments Available for a PTCH1 Mutation? Treatment There are no specific treatments for a PTCH1 mutation. Your doctor will likely recommend starting cancer testing at an earlier age and undergoing more frequent testing. Some tests they may recommend to help detect cancer or other abnormalities include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976291f9a7c2d-1442-4f25-bbba-74cacf2e3d0ce60dc2a1-f33c-4a05-9b50-8e3e8e59762904bf405d-93ee-4139-951b-28e95994fd69 X-rays Magnetic resonance imaging of the brain to check for tumors Total body skin exams Echocardiogram to check for heart fibromas Ultrasounds of the heart and ovaries Yearly hearing, vision, and speech evaluations If your doctor detects an abnormality, there are a number of specific treatment options available, including surgery, topical treatments, and medications, such as sonidegib (Zokinvy), glasdegib (Infigem), and vismodegib (Erivedge).e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c1e091f-451b-4a94-92aa-3e7094707ae5 Researchers are continually looking into potential new therapies that target the hedgehog signaling pathways. Several clinical trials are either ongoing or recently finished. As novel treatments successfully go through clinical trials, new therapies may become available to treat cancers caused by PTCH1 mutations.
The Takeaway PTCH1 mutations are rare, but they are strongly associated with Gorlin syndrome, a hereditary condition that can increase your risk of basal cell skin cancers and developmental abnormalities, as well as other types of cancer, such as nonhereditary skin cancers, breast cancer, and colon cancer. If you test positive for a PTCH1 mutation, it doesn’t mean you will develop cancer. Your doctor will likely recommend getting early and frequent cancer screenings in order to detect any growths or changes early on. Medications such as vismodegib (Erivedge) can help target cancers caused by a PTCH1 mutation.
Resources We Trust Cleveland Clinic: The Rise of Basal Cell and Squamous Cell Carcinomas: What’s the Difference? Johns Hopkins Medicine: Basal Cell Nevus Syndrome (Gorlin Syndrome) MedlinePlus: Gorlin Syndrome American Cancer Society: What Are Basal and Squamous Cell Skin Cancers? National Cancer Institute: Genetics of Skin Cancer