Whole-genome analyses of loss of heterozygosity and methylation analysis of four tumor-suppressor genes in N-methyl-N′-nitro-N-nitrosoguanidine-induced rat stomach carcinomas

Tohru Niwa, Satoshi Yamashita, Tetsuya Tsukamoto, Takashi Kuramoto, Tomoko Nomoto, Kuniko Wakazono, Hirofumi Fujita, Taijiro Matsushima, Masae Tatematsu, Takashi Sugimura, Toshikazu Ushijima

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22 Citations (Scopus)

Abstract

N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced rat stomach carcinomas are considered to be a good model for differentiated-type human stomach carcinomas. However, as for their molecular basis, only infrequent mutations of Catnb (β-catenin) and Trp53 (p53) have been observed. Here, we carried out a whole-genome analysis of loss of heterozygosity (LOH) using 21 stomach carcinomas induced by MNNG in F1 hybrids of ACI and BUF rats, and also analyzed promoter methylation of four tumor-suppressor genes. LOH analysis was performed using 130 polymorphic markers covering rat chromosomes 1-20 with an average interval of 20 Mbp. Despite adapting conditions so that LOH could be detected with up to a 50% contamination of stromal cells, no LOH was detected at any loci. CpG islands in putative promoter regions of four tumor-suppressor genes, Cdh1 (E-cadherin), Cdkn2a (p16), Mlh1, and Rassf1a, were analyzed by methylation-specific polymerase chain reaction (PCR). However, no methylation was detected. In contrast, the promoter region of Pgc (pepsinogen C), which lacks a CpG island, was methylated in all 21-cancer samples. These results indicated that LOH spanning a chromosomal region larger than 30-40 Mbp or silencing of Cdh1, Cdkn2a, Mlh1, and Rassf1a, was not involved in MNNG-induced rat stomach carcinomas. The search for other genes involved in these carcinomas needs to be continued.

Original languageEnglish
Pages (from-to)409-413
Number of pages5
JournalCancer science
Volume96
Issue number7
DOIs
Publication statusPublished - 01-07-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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