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

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.

• Authors: Hisashi Takino, Mitsukuni Okabe, Chunmei Li, Koichi Ohshima, Tadashi Yoshino, Shigeo Nakamura, Ryuzo Ueda, Tadaaki Eimoto, Hiroshi Inagaki
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 18 Issue 9 Pg. 1187-92 (Sep 2005) ISSN: 0893-3952 [Print] United States
• PMID: 15832193 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• API2-MALT1 fusion protein, human
• Oncogene Proteins, Fusion

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Methylation
• Female
• Genes, p16
• Humans
• Lung Neoplasms (genetics)
• Lymphoma, B-Cell (genetics)
• Lymphoma, B-Cell, Marginal Zone (genetics)
• Lymphoma, Large B-Cell, Diffuse (genetics)
• Male
• Middle Aged
• Mutation
• Oncogene Proteins, Fusion (genetics)
• Polymorphism, Single-Stranded Conformational
• Reverse Transcriptase Polymerase Chain Reaction