CPT® Code 81276

KRAS (Kirsten rat sarcoma viral oncogene homolog) (eg, carcinoma) gene analysis; additional variant(s) (eg, codon 61, codon 146)

The CPT® Code 81276 pertains to the molecular genetic testing of the KRAS gene, specifically focusing on the analysis of additional variants such as those found at codon 61 and codon 146. The KRAS gene is crucial as it encodes the K-Ras protein, which plays a significant role in regulating cell growth, division, maturation, and differentiation through signal transduction. This process involves the K-Ras protein acting as a GTPase, functioning like a molecular switch that toggles between an active state when bound to guanosine triphosphate (GTP) and an inactive state when it hydrolyzes GTP to guanosine diphosphate (GDP). In the presence of mutations, a single alteration in the protein structure can lead to continuous activation of the K-Ras protein, resulting in uncontrolled cell proliferation. The KRAS gene is classified within the Ras family of oncogenes and is located on chromosome 12, particularly at codons 12 or 13 in exon 2. Mutations in the KRAS gene can lead to various genetic disorders, including a severe form of Noonan syndrome, characterized by symptoms such as intellectual disability, short stature, congenital heart defects, and skeletal anomalies. Another condition associated with KRAS mutations is cardiofaciocutaneous (CFC) syndrome, which presents with similar intellectual challenges, distinctive facial features, short stature, macrocephaly, and sparse hair. Furthermore, somatic mutations of the KRAS gene are frequently observed in several malignancies, including lung, pancreatic, and colorectal cancers. Notably, mutations at codon 61, which result in a change in the amino acid glutamine, are linked to lung and colorectal cancers, while mutations at codon 146 in exon 4 are primarily associated with colorectal cancers and, less commonly, with acute myeloid leukemia and acute lymphoblastic leukemia. Additionally, the presence of mutations at codon 61 and codon 146 has been shown to predict resistance to EGFR-targeted therapies, such as cetuximab. The testing for these mutations is typically performed on blood or tissue samples using polymerase chain reaction-based Sanger sequencing of DNA, making it a vital tool in the diagnosis and management of related conditions and cancers.