Immunoglobulin VH gene analysis in gastric MALT lymphomas.
The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P=0.0094) and Group C (2/12 cases, 17%, P=0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pylori-associated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria.
Sakuma
Hidenori
H
Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Nakamura
Tsuneya
T
Uemura
Naomi
N
Chiba
Tsutomu
T
Sugiyama
Toshiro
T
Asaka
Masahiro
M
Akamatsu
Taiji
T
Ueda
Ryuzo
R
Eimoto
Tadaaki
T
Goto
Hidemi
H
Nakamura
Shigeo
S
Inagaki
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D015870:Gene Expression; D050438:Genes, Immunoglobulin Heavy Chain; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
C415943:API2-MALT1 fusion protein, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger