Figure 6.

Bisulfite genomic sequencing of the p16(CDKN2A), H-cadherin (CDH13), and APC gene promoters in normal tissues (n = 6); preneoplasia-containing tissues on months 3 to 4 (n = 5), months 6 to 8 (n = 5), and months 10 to 12 (n = 5); and nine representative lung tumors. Vertical bars show the distribution of CpG islands at p16, H-cadherin, and APC. The vertical arrow indicates the transcriptional start point. Black dots indicate methylated CpG islands; white dots indicate unmethylated CpG islands. The position of the bisulfite sequencing primers is represented with white horizontal arrows. We observed H-cadherin promoter hypermethylation in seven of nine silica-induced tumors (T1, T2, T3, T4, T5, T6, and T9), and APC promoter hypermethylation in five of nine tumors (T2, T3, T4, T5, and T9). Hypermethylation in the p16 promoter was also an important event in six of nine tumors studied (T1, T2, T3, T5, T8, and T9).