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Title:
Alteration of the p14 ARF gene and p53 status in human hepatocellular carcinomas | Journal of Gastroenterology
Description:
The INK4a/ARF locus encodes p16INK4a and p14ARF, both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16INK4a and p53/ARF. Inactivation of RB/p16INK4a was frequently reported, but alterations of the p14 ARF gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed. Methods To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14 ARF gene; alterations of p53 were also analyzed in the same series of HCCs. Results Homozygous deletion, spanning from exon 1βΞ² to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14 ARF alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alteration; however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14ARF in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P < 0.0001), and increased expression of p14ARF seemed to be associated with poorly differentiated phenotype. Absence of p14ARF expression was seen in only one HCC, with homozygous deletion of the p14 ARF gene. Conclusions Compared with p53 alteration, p14 ARF alteration does not occur frequently, but may play a role in a subset of Japanese HCCs in the early stage of hepatocarcinogenesis. On the other hand, overexpression of p14ARF was frequently observed in HCC, especially in poorly differentiated tumors, probably reflecting oncogenic stimuli in these tumors.
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Keywords {π}
article, alteration, arf, hepatocellular, parf, hccs, access, gene, privacy, cookies, content, journal, carcinoma, publish, search, hcc, expression, differentiated, open, kyoto, data, information, log, research, ito, nishida, fukuda, frequently, deletion, exon, tumors, discover, springer, optional, personal, parties, policy, find, track, gastroenterology, status, human, carcinomas, april, cite, teruaki, naoshi, yoshihiro, takafumi, nishimura,
Topics {βοΈ}
month download article/chapter hepatocellular carcinoma human hepatocellular carcinomas related subjects p14 arf gene privacy choices/manage cookies full article pdf check access instant access 1 hcc mutations p53/arf alteration p14 arf alteration european economic area tumor suppressor pathways showed immunohistochemical evidence reflecting oncogenic stimuli conditions privacy policy accepting optional cookies april 2004 volumeΒ 39 poorly differentiated phenotype article ito journal finder publish article journal mutation article log p53/arf poorly differentiated tumors article cite privacy policy personal data books a p53 alteration yoshihiro fukuda optional cookies information manage preferences p53 status journal publish subscription content similar content data protection essential cookies cookies skip p14arf expression gastroenterology aims homozygous deletion institution subscribe rb/p16ink4a usage analysis social media
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headline:Alteration of the p14 ARF gene and p53 status in human hepatocellular carcinomas
description:The INK4a/ARF locus encodes p16INK4a and p14ARF, both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16INK4a and p53/ARF. Inactivation of RB/p16INK4a was frequently reported, but alterations of the p14
ARF
gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed. To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14
ARF
gene; alterations of p53 were also analyzed in the same series of HCCs. Homozygous deletion, spanning from exon 1βΞ² to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14
ARF
alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alteration; however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14ARF in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P < 0.0001), and increased expression of p14ARF seemed to be associated with poorly differentiated phenotype. Absence of p14ARF expression was seen in only one HCC, with homozygous deletion of the p14
ARF
gene. Compared with p53 alteration, p14
ARF
alteration does not occur frequently, but may play a role in a subset of Japanese HCCs in the early stage of hepatocarcinogenesis. On the other hand, overexpression of p14ARF was frequently observed in HCC, especially in poorly differentiated tumors, probably reflecting oncogenic stimuli in these tumors.
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p14ARF
p53
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hepatocellular carcinoma
Gastroenterology
Hepatology
Abdominal Surgery
Colorectal Surgery
Surgical Oncology
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headline:Alteration of the p14 ARF gene and p53 status in human hepatocellular carcinomas
description:The INK4a/ARF locus encodes p16INK4a and p14ARF, both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16INK4a and p53/ARF. Inactivation of RB/p16INK4a was frequently reported, but alterations of the p14
ARF
gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed. To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14
ARF
gene; alterations of p53 were also analyzed in the same series of HCCs. Homozygous deletion, spanning from exon 1βΞ² to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14
ARF
alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alteration; however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14ARF in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P < 0.0001), and increased expression of p14ARF seemed to be associated with poorly differentiated phenotype. Absence of p14ARF expression was seen in only one HCC, with homozygous deletion of the p14
ARF
gene. Compared with p53 alteration, p14
ARF
alteration does not occur frequently, but may play a role in a subset of Japanese HCCs in the early stage of hepatocarcinogenesis. On the other hand, overexpression of p14ARF was frequently observed in HCC, especially in poorly differentiated tumors, probably reflecting oncogenic stimuli in these tumors.
datePublished:
dateModified:
pageStart:355
pageEnd:361
sameAs:https://doi.org/10.1007/s00535-003-1302-9
keywords:
p14ARF
p53
INK4a/ARF locus
hepatocellular carcinoma
Gastroenterology
Hepatology
Abdominal Surgery
Colorectal Surgery
Surgical Oncology
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