A20 inactivation in ocular adnexal MALT lymphoma.
Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. mqd20@cam.ac.uk
Yingwen
Y
Bi
Naiyan
N
Zeng
Estelle
E
Chanudet
Yuanxue
Y
Huang
Rifat A
RA
Hamoudi
Hongxiang
H
Liu
Gehong
G
Dong
A James
AJ
Watkins
Steven C
SC
Ley
Lifen
L
Zou
Rongjia
R
Chen
Xiongzeng
X
Zhu
Ming-Qing
MQ
Du
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000595:Amino Acid Sequence; D020169:Caspases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005134:Eye Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011839:Radiation, Ionizing; D054390:Receptors, CCR2 / Q000235:genetics; D017384:Sequence Deletion; D051216:Toll-Like Receptor 6 / Q000235:genetics; D014178:Translocation, Genetic; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D051025:bcl-Associated Death Protein / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C515334:CCR2 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D054390:Receptors, CCR2; C495368:TLR6 protein, human; C117046:TNIP1 protein, human; C434062:TNIP2 protein, human; D051216:Toll-Like Receptor 6; D051025:bcl-Associated Death Protein; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein