|DNA Change (Coding Nucleotide)
Ras-like-without-CAAX-1 (RIT1) gene is a member of the RAS gene family. Recurrent somatic mutations of RIT1 have been reported in approximately 7% of cases of chronic myelomonocytic leukemia, and less than 5% of cases of myelodysplastic syndrome and less than 5% of acute myeloid leukemia. The mutations typically occur in the Switch II effector domain, and the affected residues are close to codon Q79, which is analogous to amino acid Q61 of NRAS or KRAS where mutations frequently occur in cancer. Moreover, the experimental Q79L mutation in RIT1 has been reported to confer constitutive activation of the protein. RIT1 mutations are typically mutually exclusive of mutations in other RAS family members. In addition, RIT1 maps to the minimal common amplified region (1q21-22) in 1q gains frequently found in other cancers. 1q amplification involving the RIT1 locus has been reported in 4-18% of cases of myelofibrosis as well as less than 5% of chronic myelomonocytic leukemia, less than 5% of myelodysplastic syndromes and less than 5% of acute myeloid luekemia. In rare cases mutations and amplifcations of RIT1 may coexist. In general, RIT1 has been reported to increased phosphorylation of AKT and activate proliferation through the mitogen activated protein kinase pathway.