Multigene methylation analysis of gastrointestinal tumors: TPEF emerges as a frequent tumor-specific aberrantly methylated marker that can be detected in peripheral blood.
BACKGROUND
Gene promoter methylation is a mechanism for tumor suppressor gene silencing and inactivation. The development of highly sensitive methods for revealing aberrant cancer-associated DNA methylation allows the identification of tumor markers not only in tumor samples, but also in body fluid, an approach that can be useful in the early detection of neoplasms.


METHODS
We analyzed the methylation status at 16 loci in tumor samples of the gastrointestinal tract and in early or pre-neoplastic lesions of the colon.


RESULTS
Tumor samples revealed that methylation at the transmembrane protein containing epidermal growth factor and follistatin domains (TPEF) locus had the best ratio of discrimination between tumor samples versus normal tissues (83 versus 0%). Its combination with hypermethylated in cancer 1 (HIC1), death-associated protein kinase (DAPK) and O-6-methylguanine DNA methyltransferase (MGMT), allowed the detection of aberrant methylation in 98% of colorectal carcinomas and 100% of gastric carcinomas. The same alterations were also detected in colon adenomas and tissues surrounding the adenomas, indicating that hypermethylation at these loci occurred early in tumor progression. Analysis of DNA from peripheral blood revealed that TPEF methylation was detectable in colorectal tumor patients and patients with early or pre-neoplastic lesions, but not in healthy volunteers.


CONCLUSIONS
Our results identify TPEF as a tumor marker that could be useful in the follow-up of gastrointestinal cancer patients or the screening of individuals at risk of developing gastrointestinal neoplasms.
Sabbioni
Silvia
S
Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
Miotto
Elena
E
Veronese
Angelo
A
Sattin
Elisa
E
Gramantieri
Laura
L
Bolondi
Luigi
L
Calin
George A
GA
Gafà
Roberta
R
Lanza
Giovanni
G
Carli
Giuliano
G
Ferrazzi
Eros
E
Feo
Carlo
C
Liboni
Alberto
A
Gullini
Sergio
S
Negrini
Massimo
M
D000236:Adenoma / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm