DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type.
BACKGROUND
We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better treatment of individuals with NSCLC.


METHODS
We determined the DNA methylation status of 27 genes using quantitative MethyLight assays in lung tumor samples from 117 clinically well-characterized NSCLC patients.


RESULTS
Hypermethylation was detected in one of more of the genes in 106 (91%) of 117 cases and was detected at high levels (percentage methylation reference (PMR)> or =4%) in 79% of NSCLC cases. Methylation of APC, CCND2, KCNH5 and, RUNX was significantly more frequent in adenocarcinomas compared to squamous cell carcinomas (SCC), while methylation of CDKN2A was more common in SCC. Hypermethylation of KCNH5, KCNH8, and RARB was more frequent in females compared to males. Hypermethylation of APC and CCND2 was inversely associated with proliferation score assessed by Ki-67 level.


CONCLUSIONS
Our findings of differential gene hypermethylation frequencies in tumor tissues from patients with adenocarcinoma or squamous cell cancers and in females compared to males suggests that further investigation is warranted in order to more fully understand the potential disparate pathways and/or risk factors for NSCLC associated with histologic type and gender.
Hawes
Stephen E
SE
Department of Epidemiology, School of Public Health, University of Washington, Box 359933, Seattle, WA 98195, USA. hawes@u.washington.edu
Stern
Joshua E
JE
Feng
Qinghua
Q
Wiens
Linda W
LW
Rasey
Janet S
JS
Lu
Hiep
H
Kiviat
Nancy B
NB
Vesselle
Hubert
H
D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000235:genetics; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation; D005260:Female; D017491:Genes, APC; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
C080336:CCND2 protein, human; D056742:Cyclin D2; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D004247:DNA