HRAS gene testing and cancer
HRAS gene testing involves analyzing the HRAS gene, which encodes a protein essential for cellular growth and division. Mutations or overexpression of this gene are linked to various cancers, including bladder, breast, thyroid, and lung cancers. Additionally, HRAS mutations are significant in diagnosing Costello syndrome, a rare developmental disorder characterized by symptoms such as delayed development, distinctive facial features, and an increased risk of specific cancers. Approximately 80% of individuals with Costello syndrome exhibit HRAS mutations, making genetic testing crucial for accurate diagnosis. The testing process typically requires a blood sample, with options for prenatal screening available for at-risk parents. While the risks associated with blood sampling are minimal, genetic counseling is recommended to help patients understand the potential implications of their results. Following testing, individuals diagnosed with Costello syndrome should be monitored for certain malignancies due to their heightened cancer risk. Overall, HRAS gene testing serves as a vital tool in both cancer research and the diagnosis of related genetic conditions.
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HRAS gene testing and cancer
ALSO KNOWN AS: v-Ha-ras Harvey rat sarcoma viral oncogene homolog, Harvey murine sarcoma virus oncogene, c-H-ras, HRAS1
DEFINITION: The HRAS gene encodes a protein that allows cells to translate extracellular signals into intracellular events that induce cellular growth and division. HRAS is overexpressed or mutated to an overactive form in cancer of the bladder, breast, thyroid, lungs, and other organs. It is also mutated in individuals afflicted with Costello syndrome, a rare developmental disorder. Symptoms of Costello syndrome include delayed development; distinctive facial features; flexible joints; papilloma around the mouth, nose, and anus; heart abnormalities; and an increased susceptibility to several types of cancer, including rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma. HRAS mutations comprise 77 percent of HRAS alterations. Other alterations include HRAS Exon 2 Mutation, HRAS Codon 61 Missense, and HRAS Q61R.
Conditions diagnosed: Costello syndrome
Why performed: Costello syndrome is difficult to distinguish from other developmental disorders. Testing for mutations in HRAS is a valuable method to diagnose Costello syndrome because approximately 80 percent of patients with this disorder have mutations in HRAS. In contrast, mutations in other genes cause other syndromes. Prenatal screening is also available for parents who have children affected with Costello syndrome.
Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of testing and the significance of negative, positive, and inconclusive results.
Steps of the procedure: Material required to confirm a diagnosis of Costello syndrome is generally obtained from a blood sample. Amniotic fluid or chorionic villus sampling is required for prenatal screening. Samples are sent to a clinical laboratory that offers HRAS screening. Deoxyribonucleic acid (DNA) is purified from the sample, and the DNA that encodes HRAS is amplified by polymerase chain reaction (PCR) and sequenced using standard methods.
After the procedure: The patient will consult with a physician or genetic counselor to discuss the implications of the test results.
Risks: Complications from drawing blood are rare but may include excessive bleeding, hematoma, or infection. The risk of miscarriage due to chorionic villus sampling is estimated at 1 in 100 to 1 in 200. Because the information obtained from HRAS screening may have significant psychological effects, patients must be offered genetic counseling.
Results: Around 15 percent of individuals with Costello syndrome develop malignant tumors. Once diagnosed, patients should be monitored closely for rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma.
Bibliography
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Wey, Michael, et al. "Kinetic Mechanisms of Mutation-Dependent Harvey Ras Activation and Their Relevance for the Development of Costello Syndrome." Biochemistry, vol. 52, no. 47, 2013, pp. 8465–479. doi:10.1021/bi400679q.