This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vachtenheim, J. Articles by Novotná, H. Search for Related Content PubMed PubMed Citation Articles by Vachtenheim, J. Articles by Novotná, H.

Hypomethylation of CCGG Sites in the 3' Region of H-ras Protooncogene Is Frequent and Is Associated with H-ras Allele Loss in Non-Small Cell Lung Cancer¹

Jií Vachtenheim², Irena Horáková and Hana Novotná

Laboratory of Molecular Biology, Institute of Chest Diseases, 18071 Prague 8, Czech Republic

The methylation of MspI/HpaII sites flanking a variable tandem repeat in the 3' region of the c-Ha-ras protooncogene was analyzed in 74 DNA samples of non-small cell lung carcinomas and control lung tissues. Of 39 informative samples, 7 allelic deletions (18%) were found at the c-Ha-ras locus and of these, five (71%) showed hypomethylation of the nondeleted allele. Heterozygous DNA samples without allele loss revealed hypomethylation in 37% (12 of 32). Among 35 homozygotes, 9 showed hypomethylation (26%). We also analyzed c-Ha-ras mutations at codons 12, 13, and 61 by polymerase chain reaction and designed restriction fragment length polymorphism and found no mutation. Thus, c-Ha-ras mutations are not associated with the development of the detected abnormalities. We conclude that hypomethylation at specific sites in the 3' region is associated with loss of heterozygosity for the c-Ha-ras gene in non-small cell lung cancer. The finding that, in informative samples, hypomethylation occurs 2–3 times more frequently than allelic loss suggests that it might be a change contributing or predisposing to a genetic instability that can ultimately lead to c-Ha-ras allelic deletions found in tumor DNA.

¹ This work was supported by Grants 0072-3 and 0952-3 from the Internal Grant Agency, Ministry of Health, Czech Republic (J. V.).

² To whom requests for reprints should be addressed.

Received 11/17/93. Accepted 1/20/94.

This article has been cited by other articles:

				J. De-Castro Arce, E. Gockel-Krzikalla, and F. Rosl Retinoic Acid Receptor beta Silences Human Papillomavirus-18 Oncogene Expression by Induction of de Novo Methylation and Heterochromatinization of the Viral Control Region J. Biol. Chem., September 28, 2007; 282(39): 28520 - 28529. [Abstract] [Full Text] [PDF]

				T. Etoh, Y. Kanai, S. Ushijima, T. Nakagawa, Y. Nakanishi, M. Sasako, S. Kitano, and S. Hirohashi Increased DNA Methyltransferase 1 (DNMT1) Protein Expression Correlates Significantly with Poorer Tumor Differentiation and Frequent DNA Hypermethylation of Multiple CpG Islands in Gastric Cancers Am. J. Pathol., February 1, 2004; 164(2): 689 - 699. [Abstract] [Full Text] [PDF]

				Y. Saito, Y. Kanai, M. Sakamoto, H. Saito, H. Ishii, and S. Hirohashi Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis PNAS, July 23, 2002; 99(15): 10060 - 10065. [Abstract] [Full Text] [PDF]

				J. F Costello and C. Plass Methylation matters J. Med. Genet., May 1, 2001; 38(5): 285 - 303. [Abstract] [Full Text]