title: DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase in patients with TP53 germline mutations.
abstract: Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age of disease onset are known to vary, even in patients carrying the same mutation, and several mechanisms such as genetic and epigenetic alterations may be involved in this variability. However, the extent of involvement of such events has not been clarified. It is well established that p53 regulates several pathways, including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA methylation of several genes. This study aimed to identify the DNA methylation pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8, OCT4, SOX2, and SOX17) in 30 patients with germline TP53 mutations, 10 patients with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53 mutation. Gene methylation patterns of peripheral blood DNA samples assessed by pyrosequencing revealed no significant differences between the three groups. However, increased TDG expression was observed by quantitative reverse transcription PCR in p.R337H carriers with ADR. Considering the rarity of this phenotype and the relevance of these findings, further studies using a larger sample set are necessary to confirm our results.
authors.affiliation: CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: F P
authors.initials: FP
authors.lastname: Fortes
authors.affiliation: CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: H
authors.initials: H
authors.lastname: Kuasne
authors.affiliation: CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: F A
authors.initials: FA
authors.lastname: Marchi
authors.affiliation: CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: P M
authors.initials: PM
authors.lastname: Miranda
authors.affiliation: CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: S R
authors.initials: SR
authors.lastname: Rogatto
authors.affiliation: CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: M I
authors.initials: MI
authors.lastname: Achatz
mesh_terms: D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044502:Thymine DNA Glycosylase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044502:Thymine DNA Glycosylase