Affiliations: Department of Nutrition Sciences, University of
Alabama at Birmingham, AL 35294, USA | Department of Pathology, University of Alabama at
Birmingham, AL 35294, USA | Department of Epidemiology, University of Alabama at
Birmingham, AL 35294, USA | Laboratory of Virology, Faculty of Medicine,
University Joseph Fourier of Grenoble, Avenue Gresivaudan, 38706 La Tronche,
France
Note: [] Corresponding author: Chandrika J. Piyathilake, Department of
Nutrition Sciences, Division of Nutritional Biochemistry and Molecular Biology,
University of Alabama at Birmingham (UAB), 1675 University Blvd, Webb 318A,
Birmingham, AL 35294-3360, USA. Tel.: +1 205 975 5398; Fax: +1 205 996 2859;
E-mail: piyathic@uab.edu
Abstract: Although there is growing interest in the possibility that
alterations in histone methylation may play a role in carcinogenesis, it has
not been explored adequately in humans. Similarly, there are no reports of
associations between this and a similar epigenetic event, DNA methylation.
Using immunohistochemical staining, we compared the methylation of DNA and
histones in histopathologically normal oral epithelium, dysplastic oral
lesions, and squamous cell cancers (SCCs) from subjects with squamous cell
cancer (n=48) with those of normal oral epithelium from subjects without oral
cancer (n=93) who were matched on age and race. Monoclonal antibodies specific
for 5 methyl cytosine (5-mc), lysine 4 of histone H_3
(H_3-Lys4), and lysine 9 of histone H_3
(H_3-Lys9) were used in this study. The percentages of cells
positive and a weighted average of the immunostaining intensity scores were
calculated for each of these tissues, and Spearman correlation analyses were
employed to study associations between DNA and histone methylation.
Correlations between DNA and histone methylation, H_3-Lys4
and H_3-Lys9 were positive and statistically significant in
all tissue types; they were strongest in normal oral epithelium from non-cancer
subjects (r=0.63, p < 0.001 and r=0.62, p < 0.001 respectively). Similarly,
the positive correlations between H_3-Lys4 and
H_3-Lys9 were statistically significant in all tissue types
and strongest in normal oral epithelium from non-cancer subjects (r=0.77, p<
0.001). Patterns of DNA and histone methylation are similar in tissues across
the spectrum of oral carcinogenesis, and there is a significant positive
association between these two epigenetic mechanisms.
