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J Pathol Transl Med : Journal of Pathology and Translational Medicine

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2 "p16-DNA Methylation"
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Original Articles
Methylotion Analysis of p16/INK4A in Gastric Low-Grade Mucosa-Associated Lymphoid Tissue Lymphomas after Helicobacter pylori Eradication Therapy.
Young A Kim, Sung Shin Park, Bo Young Lee, You Sun Kim, In Sung Song, Chul Woo Kim
Korean J Pathol. 2002;36(1):13-20.
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AbstractAbstract PDF
BACKGROUND
Inactivation of p16 has been associated with promoter region hypermethylation in different types of malignancies, including non-Hodgkin's lymphomas (NHLs). This loss of p16 was found frequently in cases of mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies indicate that promoter hypermethylation is often an early event in tumor progression in the follow-up of NHLs.
METHODS
To investigate the usefulness of p16 methylation in the diagnosis and follow-up of gastric low-grade MALT lymphomas, we analyzed methylation status of p16 using methylation-specific polymerase chain reaction methods in the sequential biopsy specimens of 13 patients with gastric low-grade MALT lymphomas undergoing Helicobacter pylori eradication therapy.
RESULTS
Five of thriteen cases showed p16 hypermethylation upon diagnosis. In four of five methylation positive cases, abnormal methylation was detected in the specimen even after the treatment, although there were no histologic evidence of disease. This methylation disappeared in the later samples of two of the cases, and they have remained in complete remission. Immunohistochemically, the loss of p16 protein expression was detected in one of three methylation-positive cases, and in none of the methylation-negative cases.
CONCLUSIONS
These results suggest that p16 methylation is relatively fequent in low-grade gastric MALT lymphomas, and it may have clinical applications in the management and follow-up of low-grade gastric MALT lymphomas.
Inactivation Pattern of p16 Gene in Non-Hodgkin's Lymphomas.
Hyun Deuk Cho, In Sun Kim
Korean J Pathol. 2002;36(6):365-373.
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AbstractAbstract PDF
BACKGROUND
Loss of heterozygosity (LOH) and mutation of the p16 tumor suppressor gene have been detected in non-Hodgkin's lymphomas (NHLs). Recently, hypermethylation of the p16 gene has been reported. The role of p16 gene alterations in the genesis of NHLs and their high-grade transformations require explanation.
METHODS
LOH of D9S171 and IFNA microsatellite markers, DNA hypermethylation, and mutation of exon 1 and 2A were assessed in 43 cases of NHLs. The genetic abnormalities were compared with the protein expression by immunohistochemistry, and they were evaluated according to the histologic subtypes, grades and immunophenotypes.
RESULTS
DNA hypermethylation was the most common p16 gene abnormality and was found in 30 of 39 cases (76.9%). Eight cases (18.6%) showed LOH in one or both microsatellite markers, and five cases (11.6%) showed mutations in exon 1 or 2A. Loss of protein expression was seen in 17 cases (39.5%) and was associated with mutation and LOH. Loss of protein was more frequent in high-grade lymphomas than in low-grade lymphomas.
CONCLUSION
These results suggest that the functional loss of the p16 gene contributes to the development of NHLs, especially to the development of high-grade lymphomas.

J Pathol Transl Med : Journal of Pathology and Translational Medicine