title: A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands.
abstract: The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-kappaB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42=19%), salivary gland (2/24=8%), thyroid (1/9=11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p<0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p=0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p=0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation-negative MALT lymphoma.
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, UK.
authors.forename: E
authors.initials: E
authors.lastname: Chanudet
authors.forename: H
authors.initials: H
authors.lastname: Ye
authors.forename: J
authors.initials: J
authors.lastname: Ferry
authors.forename: C M
authors.initials: CM
authors.lastname: Bacon
authors.forename: P
authors.initials: P
authors.lastname: Adam
authors.forename: H K
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: J
authors.initials: J
authors.lastname: Radford
authors.forename: S A
authors.initials: SA
authors.lastname: Pileri
authors.forename: K
authors.initials: K
authors.lastname: Ichimura
authors.forename: V P
authors.initials: VP
authors.lastname: Collins
authors.forename: R A
authors.initials: RA
authors.lastname: Hamoudi
authors.forename: A G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: A C
authors.initials: AC
authors.lastname: Wotherspoon
authors.forename: P G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: M Q
authors.initials: MQ
authors.lastname: Du
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002896:Chromosomes, Human, Pair 6; D055028:Comparative Genomic Hybridization / Q000379:methods; D004268:DNA-Binding Proteins; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009918:Orbital Neoplasms / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics; D014178:Translocation, Genetic; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3