High frequency of simultaneous loss of p16 and p16β gene expression in squamous cell carcinoma of the esophagus but not in adenocarcinoma of the esophagus or stomach Journal Article
| Authors: | Hayashi, K.; Metzger, R.; Salonga, D.; Danenberg, K.; Leichman, L. P.; Fink, U.; Sendler, A.; Kelsen, D.; Schwartz, G. K.; Groshen, S.; Lenz, H. J.; Danenberg, P. V. |
| Article Title: | High frequency of simultaneous loss of p16 and p16β gene expression in squamous cell carcinoma of the esophagus but not in adenocarcinoma of the esophagus or stomach |
| Abstract: | Quantitative reverse transcription PCR (RT-PCR) was used to measure gene expressions (relative mRNA levels) of p16 and the alternate transcript p16β in esophageal and gastric tumors. p16 gene expression was undetectable in 13 of 25 esophageal squamous cell carcinomas. In 11 of these tumors, p16β was simultaneously missing whereas two of the p16-deficient tumors still expressed p16β. Among 34 esophageal adenocarcinomas and 11 gastric adenocarcinomas, only one tumor lacked p16 expression and all tumors expressed p16β. p16 sequences were not detectable by PCR in genomic DNA from tumors lacking both p16 and p16β mRNA, suggesting that the simultaneous loss of both gene expressions resulted from homozygous genomic deletion of the p16 gene. However, DNA from tumors that lacked p16 mRNA but expressed p16β did contain the p16 gene, consistent with loss of p16 expression in these tumors by transcriptional suppression. No point mutations in p16 cDNA were detected among 12 that were sequenced, but one p16 cDNA from a squamous cell carcinoma had a 19-base deletion, possibly indicating a splice-site mutation. Among those tumors that expressed p16 mRNA, the gene expression values of both p16 and p16β varied over a wide range. In some cases, p16 expression was detectable but low, suggesting that down-regulation of p16 expression may be used in some cases to achieve the funtional equivalent of gene deletion or transcriptional silencing. These results demonstrate that p16 expression patterns differ based on tumor histology and origin. Homozygous deletion of p16 appears to be common in esophageal squamous cell carcinomas but in adenocarcinomas, both gene deletion and transcriptional silencing of p16 were infrequent. |
| Keywords: | clinical article; human tissue; gene deletion; sequence deletion; squamous cell carcinoma; carcinoma, squamous cell; polymerase chain reaction; adenocarcinoma; reverse transcription polymerase chain reaction; gene expression; transcription, genetic; histology; messenger rna; rna, messenger; gene loss; cyclin-dependent kinase inhibitor p16; dna primers; cyclin dependent kinase inhibitor; stomach adenocarcinoma; stomach neoplasms; esophagus carcinoma; esophageal neoplasms; p16; genes, p16; humans; human; priority journal; article; esophageal tumors; p16β |
| Journal Title: | Oncogene |
| Volume: | 15 |
| Issue: | 12 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1997-09-18 |
| Start Page: | 1481 |
| End Page: | 1488 |
| Language: | English |
| PUBMED: | 9333024 |
| PROVIDER: | scopus |
| DOI: | 10.1038/sj.onc.1201295 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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