Hypermethylation of a 5′ CpG island of p16 is a frequent event in non-Hodgkin’s lymphoma

Martı́nez-Delgado, Beatriz; Fernández‐Piqueras, José; García, María J.; Arranz, Eva; Gallego, Jorge; Rivas, Carmen; Robledo, Mercedes; Benı́tez, Javier

doi:10.1038/sj.leu.2400579

Cited by 80 publications

(59 citation statements)

References 3 publications

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“…22 The p16 INK4A gene is frequently methylated in non-Hodgkin's leukemia, a malignancy common in AIDS patients. [31][32][33] Because these studies relied on an integrasedeficient HIV-1 strain (IN D116N ), integration into the host genome does not appear necessary to elicit these epigenetic changes. 22 This work also demonstrated that HIV-1 infection of T cells causes a ~4-fold increase in DNMT1 expression, without commensurate changes in the expression of DNMT3α or DNMT3β.…”

Section: Introductionmentioning

confidence: 99%

The early expressed HIV-1 genes regulate DNMT1 expression

Youngblood¹,

Reich²

2008

Epigenetics

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Section: Introductionmentioning

confidence: 99%

The early expressed HIV-1 genes regulate DNMT1 expression

Youngblood¹,

Reich²

2008

Epigenetics

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“…Consequently, gene methylation was a major occurrence among p16 gene alterations in our study, which is in accord with previous reports. [10][11][12][13][14][15][16] Gene deletion is another means of p16 gene silencing, but has been rare in MALT lymphomas. 32,33 We attempted to detect p16 gene deletions using seven microsatellite markers, 16,34 however, most of the cases were not amplifiable or informative.…”

Section: Discussionmentioning

confidence: 99%

“…p16 gene has been considered as a tumor-suppressor gene, and among CDK inhibitors, only p16 gene is frequently silenced in a variety of tumors by epigenetic or genetic abnormalities including promoter CpG methylation and less frequently, allelic loss and gene mutation. 10,11 In lymphoid malignancies, p16 gene silencing, mainly induced by gene methylation, is frequently found in Hodgkin and non-Hodgkin lymphomas, [12][13][14] and has been associated with tumor progression. [15][16][17][18][19] However, it has also been suggested that the methylation of this gene is one of the early events in the development of lymphoid malignancies.…”

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confidence: 99%

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

Takino

Okabe

et al. 2005

Modern Pathology

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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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“…7 Previous reports have shown that inactivation of tumor suppressor genes by methylation is important in the development and malignant transformation of EMZLs. [8][9][10][11][12] However, because of its rarity, methylation studies have not been described in colorectal EMZLs.…”

mentioning

confidence: 99%

Methylation and API2/MALT1 fusion in colorectal extranodal marginal zone lymphoma

et al. 2009

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Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is rarely found in the large intestine. Because of its rarity, the underlying epigenetic and genetic changes in the pathogenesis and prognostic factors have yet to be well established. For this purpose, methylation profiles and API2/MALT1 fusion in marginal zone B-cell lymphoma of MALT in the colorectum were studied and compared with treatment outcomes. For methylation analyses, 7 independent CpG islands (p15, p16, DAP kinase, hMLH1, MINT1, MINT2, and MINT31) were examined and RT-PCR for detection of API2/MALT1 fusion transcripts were performed in 15 colorectal marginal zone B-cell lymphoma of MALT in a single institution. Marginal zone B-cell lymphomas of MALT from both gastric and colorectal locations were also examined. In methylation analyses (n ¼ 13), 8 of 13 (62%) cases were classified as CIMP (CpG island methylator phenotype)-positive. Methylation was more frequently observed in cases with advanced disease stages than with earlier stages; an average of two methylated loci for earlier stages (IE or IIE) versus four loci in advanced ones (IVE; P ¼ 0.02). The estimated 5-year progression-free survival was 42% for CIMP-positive and 100% for CIMP-negative cases (P ¼ 0.03). API2/MALT1 fusion transcripts were found in two of nine cases (22%). In two cases with concurrent gastric and colorectal involvement of marginal zone B-cell lymphoma of MALT, methylation patterns and API2/MALT1 fusion results were different by location. Our results suggest that methylation profiles define a clinically more aggressive subgroup and multiclonal origin for marginal zone B-cell lymphoma of MALT with multiorgan involvement.

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Hypermethylation of a 5′ CpG island of p16 is a frequent event in non-Hodgkin’s lymphoma

Cited by 80 publications

References 3 publications

The early expressed HIV-1 genes regulate DNMT1 expression

The early expressed HIV-1 genes regulate DNMT1 expression

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

Methylation and API2/MALT1 fusion in colorectal extranodal marginal zone lymphoma

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