CPT® Code 81317

PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

The CPT® Code 81317 pertains to the molecular genetic testing of the PMS2 gene, which is crucial for identifying specific mutations that increase an individual's risk of developing hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. The PMS2 gene is located on chromosome 7 and plays a vital role in the DNA repair process by providing instructions for producing proteins that are essential for correcting DNA errors. When mutations occur in the PMS2 gene, they can lead to the production of an abnormally short or inactive PMS2 protein, which is less effective at repairing DNA. This inefficiency results in the accumulation of unrepaired DNA errors over time, ultimately allowing for the uncontrolled proliferation of cells that can develop into tumors. Individuals with PMS2 mutations are at an increased risk not only for colorectal cancer but also for other types of cancer, including certain brain tumors associated with a variant form of Lynch syndrome known as Turcot syndrome. This condition is characterized by the presence of glioblastoma, a type of brain tumor, alongside colorectal cancer. It is important to note that some individuals may develop HNPCC 'de novo,' meaning the mutation arises spontaneously in the germ cells or fertilized egg, rather than being inherited from a parent. The full sequence analysis performed under CPT® Code 81317 involves a comprehensive examination of the PMS2 gene to identify any mutations, including point mutations or single nucleotide polymorphisms. This analysis is particularly challenging due to the presence of pseudogenes, which are non-functional copies of the PMS2 gene that can complicate the identification of true mutations. The testing process may also include the evaluation of familial variants and duplication/deletion variants, as indicated by related CPT® codes 81318 and 81319, to assess the risk factors for family members who may share the same genetic mutation. Additionally, immunohistochemistry (IHC) may be utilized on tumor tissues to evaluate the presence or absence of specific proteins, further aiding in the understanding of the genetic landscape associated with PMS2 mutations.