p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis

Hisashi Takino, Mitsukuni Okabe, Chunmei Li, Koichi Ohshima, Tadashi Yoshino, Shigeo Nakamura, Ryuzo Ueda, Tadaaki Eimoto, Hiroshi Inagaki

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.

Original languageEnglish
Pages (from-to)1187-1192
Number of pages6
JournalModern Pathology
Volume18
Issue number9
DOIs
Publication statusPublished - Sep 2005

Fingerprint

p16 Genes
Marginal Zone B-Cell Lymphoma
Methylation
Lung
Lymphoma, Large B-Cell, Diffuse
Neoplasms
Mutation
Lymphoid Tissue
Reverse Transcription
Mucous Membrane
Polymerase Chain Reaction
Serum

Keywords

  • API2-MALT1 fusion
  • Gene methylation
  • Lung
  • MALT lymphoma
  • P16/INK4a gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis. / Takino, Hisashi; Okabe, Mitsukuni; Li, Chunmei; Ohshima, Koichi; Yoshino, Tadashi; Nakamura, Shigeo; Ueda, Ryuzo; Eimoto, Tadaaki; Inagaki, Hiroshi.

In: Modern Pathology, Vol. 18, No. 9, 09.2005, p. 1187-1192.

Research output: Contribution to journalArticle

Takino, H, Okabe, M, Li, C, Ohshima, K, Yoshino, T, Nakamura, S, Ueda, R, Eimoto, T & Inagaki, H 2005, 'p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis', Modern Pathology, vol. 18, no. 9, pp. 1187-1192. https://doi.org/10.1038/modpathol.3800400
Takino, Hisashi ; Okabe, Mitsukuni ; Li, Chunmei ; Ohshima, Koichi ; Yoshino, Tadashi ; Nakamura, Shigeo ; Ueda, Ryuzo ; Eimoto, Tadaaki ; Inagaki, Hiroshi. / p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis. In: Modern Pathology. 2005 ; Vol. 18, No. 9. pp. 1187-1192.
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abstract = "p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42{\%}) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60{\%}) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55{\%}). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.",
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