Alterations of the human gene TET2 have been observed in many cancers, including lung adenocarcinoma, colon adenocarcinoma, acute myeloid leukemia, and myelodysplastic syndromes. TET2 encodes a methylcytosine dioxygenase that plays a role in epigenetic transcriptional regulation. There is a single orthologous gene in Drosophila, Tet, however, this disease model does not make use of the Drosophila ortholog.
Multiple UAS constructs of the mouse Mmus\Tet2 gene have been introduced into flies, including wild-type and variants analogous to those associated with cancer in human. See the 'Disease-Implicated Variants' table below. The TET2:p.Arg1261Cys variant is frequently observed in acute myeloid leukemias and related cancers (see https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=82394196). The TET2:p.Arg43Gly has been observed in a patient with diffuse intrinsic pontine glioma. Expression of wild-type and variant mouse genes has been induced in larval hemocytes and adult heads, resulting in cancer-related phenotypes. Transcriptomic profiles have allowed identification of genes and pathways involved in tumorigenesis as a result of TET2 dysregulation.
[updated May 2023 by FlyBase; FBrf0222196]
TET2 is altered in 4-5% of all cancers, with the greatest prevalence of alterations observed in lung adenocarcinoma, colon adenocarcinoma, acute myeloid leukemia, myelodysplastic syndromes, and cutaneous melanoma; TET2 alterations are observed in 14% of acute myeloid leukemia patients and 3.4% of glioblastoma patients (https://www.mycancergenome.org/content/gene/tet2).
TET2 encodes a dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. [Gene Cards, TET2; 2023.09.06]
Many to one: 3 human genes to 1 Drosophila gene.
