Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer.
The serine protease family member PRSS3 (trypsinogen-IV) has been implicated as a putative tumor suppressor gene due to its loss of expression, which is correlated with promoter hypermethylation, in esophageal squamous cell carcinoma and gastric adenocarcinoma. As epigenetic alteration is common in non-small cell lung cancer (NSCLC), we sought to determine if promoter hypermethylation of PRSS3 occurred in this disease, and if it was associated with clinical features of NSCLC or tobacco-related exposures in these patients. Using methylation-specific PCR, we determined the promoter hypermethylation status of PRSS3 in a case series study of primary NSCLC, and found methylation of this gene to be common, occurring in 53% (86 of 166) of tumors examined. There was no association of this alteration with patient demographics, tumor features, or exposure histories of the patients. The lack of association is of interest, as it may suggest a lack of specific selection for inactivation of this gene. On the other hand, the high prevalence of this alteration makes PRSS3 methylation an attractive biomarker for use in diagnostic or screening applications in NSCLC.
Marsit
Carmen J
CJ
Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Okpukpara
Chinedu
C
Danaee
Hadi
H
Kelsey
Karl T
KT
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012907:Smoking; D014357:Trypsin / Q000235:genetics*; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; C040749:PRSS3 protein, human; D014357:Trypsin