title: 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.affiliation: Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takino
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Okabe
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Eimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C415943:API2-MALT1 fusion protein, human; D015514:Oncogene Proteins, Fusion