Alterations and hypermethylation of the p14(ARF) gene in gastric cancer

Citation
S. Iida et al., Alterations and hypermethylation of the p14(ARF) gene in gastric cancer, INT J CANC, 87(5), 2000, pp. 654-658
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
0020-7136 → ACNP
Volume
87
Issue
5
Year of publication
2000
Pages
654 - 658
Database
ISI
SICI code
0020-7136(20000901)87:5<654:AAHOTP>2.0.ZU;2-X
Abstract
p14(ARF), generated through an alternative splicing process that replaces t he first exon, 1 alpha, of p16(INK4a) with exon 1 beta, located >15 kb upst ream of exon lot, has been shown to function as a growth suppressor. We exa mined ii gastric cancer cell lines for mRNA expression, homozygous deletion , mutation, and promoter methylation of the p14(ARF) gene, No mRNA expressi on was detected in 5 of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a tow level of expression. Of the 5 cell lines without expression, 3 (MKN45, NUGC-2, a nd NUGC-4) and I (KATO III) displayed homozygous deletion and methylation o f the p14(ARF) gene, respectively. No mutation was found in the whole codin g region of the p14(ARF) gene in 8 cell lines without homozygous deletion. Our results indicate that the p14(ARF) gene is more frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer cell l ines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022), When we also an alyzed 62 primary gastric cancers for the methylation status of the p14(ARF ) promoter region, the methylation frequency tended to be higher in diffuse -type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%). T hus, p14(ARF) alterations might be involved in diffuse-type gastric carcino genesis. (C) 2000 Wiley-Liss, Inc.