title: Methylation and API2/MALT1 fusion in colorectal extranodal marginal zone lymphoma.
abstract: 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=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=0.02). The estimated 5-year progression-free survival was 42% for CIMP-positive and 100% for CIMP-negative cases (P=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.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Dong H
authors.initials: DH
authors.lastname: Sinn
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Eui J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008221:Lymphoid Tissue / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C415943:API2-MALT1 fusion protein, human; D015514:Oncogene Proteins, Fusion