Open AccessWhole‐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
Author(s) -
Niwa Tohru,
Yamashita Satoshi,
Tsukamoto Tetsuya,
Kuramoto Takashi,
Nomoto Tomoko,
Wakazono Kuniko,
Fujita Hirofumi,
Matsushima Taijiro,
Tatematsu Masae,
Sugimura Takashi,
Ushijima Toshikazu
Publication year - 2005
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2005.00068.x
Subject(s) - loss of heterozygosity , biology , methylation , tumor suppressor gene , microbiology and biotechnology , cdh1 , cdkn2a , cdkn2b , dna methylation , cancer research , cpg site , gene , carcinogenesis , genetics , allele , gene expression , cadherin , cell
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 F 1 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. ( Cancer Sci 2005; 96: 409 – 413)