MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation

[Guest guest]

Blank

Blood First Edition Paper, prepublished online December 29, 2006; DOI

10.1182/blood-2006-06-030494.

Submitted June 21, 2006

Accepted December 6, 2006

MALT lymphoma and extranodal diffuse large B-cell lymphoma are

targeted by aberrant somatic hypermutation

JA Deutsch, Ariane Aigelsreiter, Philipp B Staber, Alfred

Beham, Werner Linkesch, Christian Guelly, Ruth I Brezinschek, Margareta

Fruhwirth, Werner Emberger, Maike Buettner, Beham-Schmid, and

Neumeister*

Division of Hematology, Institute of Pathology, & Centre for Medical

Research, Institute Medical Biology & Human Genetics, Medical University Graz,

Graz, Austria

Friedrich- Unversitat, Erlangen, Germany

* Corresponding author; email: peter.neumeister@... .

Recently, a novel mechanism introducing genetic instability - termed

aberrant somatic hypermutation (ASHM) - has been described in diffuse large

B-cell lymphoma. To further investigate whether ASHM also occurs in MALT

lymphoma, we studied the mutation profile of PIM-1, PAX-5, RhoH/TTF and c-MYC in

17 MALT lymphomas and 17 extranodal DLBCL still exhibiting a low grade MALT

lymphoma component (transformed MALT lymphoma). Mutations in one or more genes

were detected in 13/17 (76.5%) cases of MALT lymphomas and in all of 17 (100%)

cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of

34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further in PIM-1

and c-MYC some of the mutations were found to affect coding exons, leading to

amino acid exchanges, thus potentially altering gene function. Expression levels

of activation-induced cytidine deaminase (AID), an enzyme essential for somatic

hypermutation (SHM) was associated with the mutational load. These data indicate

that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma,

likewise. By mutating regulatory and coding sequences of the targeted genes ASHM

may represent a major contributor to their pathogenesis.