Genetic abnormalities in gastric mucosa-associated lymphoid tissue lymphoma: Reveal by FISH, CGH and SKY
Authors: Wen-Hui Weng, Sung-Hsin Kuo, Wan-Pei Wang, Ann-Lii Cheng, Li-Tzong Chen
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

A32 

Although t(11;18)(q21;q21) is one of the most important predictors of Helicobacter pylori ( HP ) -independence in gastric MALT lymphomas, only 50% to 60% of HP-independent cases harbor this genetic aberration. Previously, we have demonstrated that nuclear expression of BCL10 and NF-κB was closely associated with HP - independent status of the gastric MALT lymphoma, irrespective of t(11;18)(q21;q21). Recent studies have demonstrated that TNF-receptor associated factor2 (TRAF2) and CARD9 are known adaptor molecules which interact with BCL10 and thereby active NF-κB. Aim of the study to investigate whether the genetic abnormalities of TRAF2, and CARD9 using fluorescence in situ hybridization (FISH) was associated with the nuclear expression of BCL10 and NF-κB in gastric MALT lymphoma.    In this study, we performed FISH on tumor samples from 14 patients who received surgical treatment for gastric MALT lymphoma to identify the role of translocation fusion genes API2/MALT1, TRAF2, and CARD9. Furthermore, in order to reveal global genetic abnormalities, the comparative genomic hybridization (CGH) and spectral karyotyping (SKY) have been performed on a cell line MALT-1 from one HP-independent MALT lymphoma patient. t(11;18)(q21;q21), a marker of H. pylori -independent MALT lymphoma, was also analyzed by RT-PCR. The expression of BCL10 and NF-κB was determined by immunohistochemistry.    At a median follow-up of 11.5 years, only one patient had evidence of tumor recurrence. Five patients with t(11;18)(q21;q21) in the tumor cells were disease-free at 9.2~12.6 years; and these patients had no abnormality of TRAF2, and CARD9. In contrast to t(11;18)(q21;q21)-positive patients, genomic again of either CARD9 or TRAF2 was found in 4 of 9 t(11;18)(q21;q21)-negative patients. Furthermore, the nuclear expression of BCL10 was found in 5 of 5 t(11;18)(q21;q21)-positive patients and 3 of 4 CARD9/ TRAF2-positive patients; and the nuclear expression of NF-κB was detected in 4 of 5 t(11;18)(q21;q21)-positive patients, 3 of 4 CARD9/TRAF2-positive patients, and 1 of 5 t(11;18)(q21;q21)-negative and CARD9/TRAF2-negative patients. Investigation on the whole genomic imbalance of one t(11;18)(q21;q21)-negative, HP-independent MALT lymphoma cell-line (MALT1 cells), the SKY karyotypes displayed a diploid chromosome content (48 XY), with ten different translocation derivative chromosomes, including t(14;18)(q32; q21), and t(3;6)(q27;q15), and two numerical alterations. Further CGH confirmed that four chromosome contained gain on the region 8q24.3, loss on the region 5p12, 7q11.21-11.22, 9p12-13.1, 9q13-21.13 in this MALT1 cell line.    Our findings indicate that genetic abnormalities (segregation, amplification, and translocation) of TRAF2 and CARD9 were found in the majority of t(11;18)(q21;q21)-negative but not in t(11;18)(q21;q21)-positive gastric MALT lymphoma patients. Furthermore, those genetic abnormalities of TRAF2 and CARD9 were closely associated with nuclear expression of BCL10 and NF-κB, suggesting these two molecules may be involved in the HP-independence of t(11;18)(q21;q21)-negative gastric MALT lymphoma patients.