Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer.
The serum of cancer patients often harbors increased free DNA levels, which can potentially be used for cancer detection. Because genetic and epigenetic alterations of the adenomatous polyposis coli (APC) gene are common events in gastrointestinal tumor development, we sought to investigate the frequency and level of aberrant APC promoter methylation in primary tumors and paired preoperative serum or plasma samples of lung cancer patients by semiquantitative methylation-specific fluorogenic real-time PCR. We detected methylation of APC in 95 of 99 (96%) primary lung cancer tissues. Forty-two of 89 (47%) available serum and/or plasma samples from these cases carried detectable amounts of methylated APC promoter DNA. In contrast, no methylated APC promoter DNA was detected in serum samples from 50 healthy controls. A highly elevated APC methylation level in lung cancer tissue was the only independent factor predicting inferior survival in this cohort (P = 0.015). APC methylation analysis appears to be promising as a prognostic factor in primary lung cancer and as a noninvasive tumor marker in plasma and/or serum DNA.
Usadel
Henning
H
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore Maryland 21205-2196, USA.
Brabender
Jan
J
Danenberg
Kathy D
KD
Jerónimo
Carmen
C
Harden
Susan
S
Engles
James
J
Danenberg
Peter V
PV
Yang
Stephen
S
Sidransky
David
D
D000368:Aged; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000378:metabolism*; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D015996:Survival Rate
D004273:DNA, Neoplasm