Inactivation of the CDKN2 gene by homozygous deletion and de novo methylation is associated with advanced stage esophageal squamous cell carcinoma.
We examined the genomic status of the CDKN2 gene including de novo methylation of 5' CpG islands in primary and metastatic tumor samples from 31 patients with esophageal squamous cell carcinoma. One somatic frame shift mutation (1 of 31; 3.2%) was identified by PCR-single strand conformational polymorphism analysis and DNA sequencing. Homozygous deletion and de novo methylation of the gene were confirmed in 5 (16%) and 6 (19%) of 31 patients, respectively. Homozygous deletion and de novo methylation were significantly associated with silencing of gene expression (P < 0.01). Aberrations of the CDKN2 gene were detected in tumors with lymph node metastasis and muscular invasion (12 of 22; 54%) and in none of stage I tumors (0 of 9.0%; P < 0.05). These results suggest that homozygous deletion and de novo methylation are predominant mechanisms of inactivation of the CDKN2 gene and may be associated with metastatic and invasive phenotypes of esophageal squamous cell carcinoma.
Maesawa
C
C
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Tamura
G
G
Nishizuka
S
S
Ogasawara
S
S
Ishida
K
K
Terashima
M
M
Sakata
K
K
Sato
N
N
Saito
K
K
Satodate
R
R
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006720:Homozygote; D006801:Humans; D008207:Lymphatic Metastasis; D008745:Methylation; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm