DNA methylation in small lung adenocarcinoma with bronchioloalveolar carcinoma components.
We examined the methylation status in 100 specimens of lung adenocarcinomas measuring 2cm or less and with bronchioloalveolar carcinoma (BAC) components (Noguchi types A-C) and then compared the methylation status between noninvasive tumors (Noguchi type A or B) and invasive tumors (Noguchi type C). Methylation-specific PCR was used to determine the methylation statuses of p16(INK4a), RASSF1A, CDH13, RARbeta, and Cyclin D2. The methylation index that was regarded as representing the degree of methylation was calculated. We also determined the mutational statuses of EGFR exons 19 and 21 using a PCR-based method. A multivariate analysis showed that the aberrant methylation of p16(INK4a), RASSF1A, and CDH13 was significantly more frequent in invasive tumors than in noninvasive tumors [p16(INK4a), 36.5% versus (vs.) 8.3%, P=0.0023; RASSF1A, 46.2% vs. 14.6%, P=0.0012; CDH13, 42.3% vs. 10.4%, P=0.0006]. The methylation index was significantly higher in invasive tumors than in noninvasive tumors (P=0.004). The methylation of p16(INK4a) was significantly more frequent in EGFR wild-type tumors than in EGFR mutant tumors (P=0.021). Our results indicate the involvement of epigenetic alterations in the progression of adenocarcinoma with BAC components.
Kubo
Takafumi
T
Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Yamamoto
Hiromasa
H
Ichimura
Koichi
K
Jida
Masaru
M
Hayashi
Tatsuro
T
Otani
Hiroki
H
Tsukuda
Kazunori
K
Sano
Yoshifumi
Y
Kiura
Katsuyuki
K
Toyooka
Shinichi
S
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000378:metabolism; D018450:Disease Progression; D005091:Exons; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics; D019942:Genes, p16; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
C080336:CCND2 protein, human; D015820:Cadherins; D056742:Cyclin D2; D004273:DNA, Neoplasm; C099972:H-cadherin; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta