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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2373-2383.
Prepublished online as a Blood First Edition Paper on June 13, 2006; DOI 10.1182/blood-2006-05-022517.
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Submitted January 12, 2006
Accepted May 22, 2006
High BCL6 expression predicts better prognosis,
independent of BCL6 translocation status, translocation
partner, or BCL6 deregulating mutations, in gastric
lymphoma
Yun-Wen Chen, Xiao-Tong Hu, Anthony C Liang, Wing-Yan Au, Chi-Chiu So, Michelle L Wong, Lijun Shen, Qian Tao, Kent-Man Chu, Yok-Lam Kwong, Raymond H Liang, and Gopesh Srivastava*
Departments of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Departments of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong
Departments of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
* Corresponding author; email: gopesh{at}pathology.hku.hk.
To investigate the role of BCL6 in the pathogenesis of
gastric lymphoma, we analyzed the BCL6 promoter region
for BCL6 translocations, somatic hypermutations, and
deregulating mutations in 43 gastric lymphomas, including
4 MALT (mucosa-associated lymphoid tissue) lymphoma, 33
DLBCL (diffuse large B-cell lymphoma), and 6 DLCLML
(composite DLBCL with residual MALT lymphoma). BCL6
promoter substitutions by immunoglobulin (Ig) and non-Ig
translocation partners, resulting in its deregulation,
were frequently involved in DLBCL (36.4%) and DLCLML
(50%). Two novel BCL6 translocation partner genes, 28S
rRNA and DMRT1, and a new BCL6 translocation breakpoint
in intron 2 were also identified. Deregulating mutations
were found only in DLBCL (24.2%), which correlated
significantly with high BCL6 protein expression.
Significantly, high BCL6 expression correlated strongly
with longer overall survival (OS), independent of
mechanism in gastric DLBCL and DLCLML. Gastric DLBCL were
further subclassified into GCB (germinal centre B-cell-
like) and non-GCB subgroup immunohistochemically. High
BCL6 expression was detected in all GCB cases,
irrespective of BCL6 genetic alterations. In the non-GCB
subgroup, BCL6 deregulating mutations correlated
significantly with high BCL6 expression level. No
significant correlation was found between the BCL6
expression level and OS in the non-GCB subgroup, which
had significantly poorer prognosis than the GCB subgroup.

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