Splenic marginal zone lymphoma: Characterization of 7q deletion and its value in diagnosis

A. James Watkins, Yuanxue Huang, Hongtao Ye, Estelle Chanudet, Nicola Johnson, Rifat Hamoudi, Hongxiang Liu, Gehong Dong, Ayoma Attygalle, Ellen D. McPhail, Mark E. Law, Peter G. Isaacson, Laurence De Leval, Andrew Wotherspoon, Ming Qing Du

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The diagnosis of splenic marginal zone lymphoma (SMZL) is frequently a challenge, due to its lack of specific histological features and immunophenotypic markers, and the existence of other poorly characterized splenic lymphomas defying classification. Moreover, the clinical outcome of SMZL is variable, with 30% of cases pursuing an aggressive clinical course, the prediction of which remains problematic. Thus, there is a real need for biomarkers in the diagnosis and prognostication of SMZL. To search for genetic markers, we comprehensively investigated the genomic profile, TP53 abnormalities, and immunoglobulin heavy gene (IGH ) mutation in a large cohort of SMZLs. 1 Mb resolution array comparative genomic hybridization (aCGH) on 25 SMZLs identified 7q32 deletion (44%) as the most frequent copy number change, followed by gains of 3q (32%), 8q (20%), 9q34 (20%), 12q23-24 (8%), and chromosome 18 (12%), and losses of 6q (16%), 8p (12%), and 17p (8%). Highresolution chromosome 7 tile-path aCGH on 17 SMZLs with 7q32 deletion identified by 1 Mb aCGH or interphase FISH screening mapped the minimal common deletion to a 3 Mb region at 7q32.1-32.2. Although it is not yet possible to identify the genes targeted by the deletion, interphase FISH screening showed that the deletion was seen in SMZL (19/56 = 34%) and splenic B-cell lymphoma/leukaemia unclassifiable (3/9 = 33%), but not in 39 cases of other splenic lymphomas including chronic lymphocytic leukaemia (n = 14), hairy cell leukaemia (4), mantle cell lymphoma (12), follicular lymphoma (6), and others. In SMZL, 7q32 deletion was inversely correlated with trisomy 18, but not associated with other copy number changes, TP53 abnormalities, or IGH mutation status. None of the genetic parameters examined showed significant and independent association with overall or eventfree survival. In conclusion, 7q32 deletion is a characteristic feature of SMZL, albeit seen in isolated cases of splenic B-cell lymphoma/leukaemia unclassifiable, and its detection may help the differential diagnosis of splenic B-cell lymphomas.

Original languageEnglish (US)
Pages (from-to)461-474
Number of pages14
JournalJournal of Pathology
Volume220
Issue number4
DOIs
StatePublished - Mar 1 2010

Keywords

  • 7q deletion
  • Array comparative genomic hybridization
  • Splenic marginal zone lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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