Multigene Methylation Analysis of Gastrointestinal TumorsTPEFEmerges as a Frequent Tumor-Specific Aberrantly Methylated Marker that Can Be Detected in Peripheral Blood
作者:
Silvia Sabbioni,
Elena Miotto,
Angelo Veronese,
Elisa Sattin,
Laura Gramantieri,
Luigi Bolondi,
George A Calin,
Roberta Gafà,
Giovanni Lanza,
Giuliano Carli,
Eros Ferrazzi,
Carlo Feo,
Alberto Liboni,
Sergio Gullini,
Massimo Negrini,
期刊:
Molecular Diagnosis
(ADIS Available online 2003)
卷期:
Volume 7,
issue 3
页码: 201-207
ISSN:1084-8592
年代: 2003
出版商: ADIS
关键词: Genetic polymorphism;Gastrointestinal cancer, diagnosis
数据来源: ADIS
摘要:
BackgroundGene 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.MethodsWe analyzed the methylation status at 16 loci in tumor samples of the gastrointestinal tract and in early or pre-neoplastic lesions of the colon.ResultsTumor 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) andO-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 thatTPEFmethylation was detectable in colorectal tumor patients and patients with early or pre-neoplastic lesions, but not in healthy volunteers.ConclusionsOur results identifyTPEFas 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.
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