PTCH1 Biomarker

The PTCH1 gene is a tumor suppressor gene that contains the instructions for making the patched-1 protein. The gene encodes a member of the patched family of proteins and is a component of the hedgehog signaling pathway. PTCH1 is a frequently altered gene in colorectal cancers (CRC) and its mutations contribute to unregulated Hedgehog (Hh) signaling resulting in uncontrolled cellular growth and tumor development.  Preliminary clinical research has revealed that patients harboring PTCH1 loss of function mutations (the protein is inactive) are more sensitive to targeted therapies. Although there are no FDA approved therapies targeting PTCH1 mutations to date, there is a clinical trial investigating the efficacy of a potential treatment in cancer patients with PTCH1 Loss of function mutations.

PTCH1 is altered in approximately 4.85% of colorectal carcinoma patients.

Some mutations are acquired during a person's lifetime and are present only in certain cells. These genetic changes, called somatic mutations, are not inherited. Somatic mutations in both copies of the PTCH1 gene are associated with non-hereditary (sporadic) types of cancer, including colorectal cancer. 

The most common PTCH1 mutations result in loss of function (LOF) of the patched-1 protein creating a constantly active state of the hedgehog signaling pathway leading to cancerous cells and tumor growth.
 

A sample of the resected tumor or biopsy sample is analyzed using DNA and RNA sequencing methods. The most common DNA sequencing methods include whole genome sequencing, whole exome sequencing or diagnostic panels that include known cancer biomarkers. Biomarker testing should be done on the primary tumor and any subsequent metastases with comprehensive genomic testing.

Knowing your biomarker status will guide you and your doctor as you choose the personalized treatment plan that will work best for your cancer. Although there are no FDA approved therapies targeting PTCH1 mutations to date, there is a clinical trial investigating the efficacy of a potential treatment in cancer patients with PTCH1 Loss of Function mutations. Consult with your oncologist about your eligibility to participate in a clinical trial as trial matching services can assist in identifying available trials based on your tumor’s biomarker results.