| First Author | Boudra R | Year | 2022 |
| Journal | J Invest Dermatol | Volume | 142 |
| Issue | 5 | Pages | 1270-1279.e2 |
| PubMed ID | 34695415 | Mgi Jnum | J:366621 |
| Mgi Id | MGI:8204851 | Doi | 10.1016/j.jid.2021.09.026 |
| Citation | Boudra R, et al. (2022) Regulation of 5-Hydroxymethylcytosine by TET2 Contributes to Squamous Cell Carcinoma Tumorigenesis. J Invest Dermatol 142(5):1270-1279.e2 |
| abstractText | DNA methylation is a key regulatory event controlling a variety of physiological processes and can have dramatic effects on gene transcription. Methylated cytosine (5-methylcytosine) can be oxidized by the TET family of enzymes to 5-hydroxymethylcytosine (5-hmC), a key intermediate in the demethylation cycle, and 5-hmC levels are reduced in malignancies such as acute myeloid leukemia and melanoma. We constructed a tissue microarray of human cutaneous squamous cell carcinoma tumors and found a global reduction in 5-hmC levels compared with that in the adjacent skin. Using a murine K14-CreER system, we have found that loss of Tet2 promotes carcinogen-induced squamous cell carcinoma and cooperates with loss of Tp53 to drive spontaneous squamous cell carcinoma tumors in epithelial tissues. Analysis of changes in 5-hmC and gene expression after loss of Tet2 in the epidermis revealed focal alterations in 5-hmC levels and an increase in hair follicle transient amplifying cell genes along with a reduction in epidermal differentiation genes. These results show a role for TET2 in epidermal lineage specification, consistent with reported roles for TET enzymes in controlling lineage commitment in hematopoietic stem cells and embryonic stem cells and establishing TET2 as a bone fide tumor suppressor in squamous cell carcinoma. |
