Molecular characterization of primary mediastinal B cell lymphoma.

TitleMolecular characterization of primary mediastinal B cell lymphoma.
Publication TypeJournal Article
Year of Publication1996
AuthorsTsang P, Cesarman E, Chadburn A, Liu YF, Knowles DM
JournalAm J Pathol
Date Published1996 Jun
KeywordsAdolescent, Adult, Blotting, Southern, DNA Mutational Analysis, Exons, Female, Gene Rearrangement, Genes, p53, Genome, Viral, Herpesvirus 4, Human, Humans, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Male, Mediastinal Neoplasms, Middle Aged, Polymorphism, Single-Stranded Conformational, Proto-Oncogenes, Retrospective Studies

Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell lymphoma (DLCL) postulated to arise from noncirculating thymic B lymphocytes. Because of its distinctive clinical and morphological features and putative unique cellular origin, PMBL is generally considered a distinct clinicopathological entity. Little is known, however, about the molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs for molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ras, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, which are commonly involved in lymphoid neoplasia. Employing a combination of Southern blotting and/or polymerase chain reaction and single-strand conformation polymorphism assays, we detected genetic alterations in 7 of the 16 (44%) PMBLs. Whereas the bcl-6 gene is rearranged in up to 45% of DLCLs, rearrangement of the bcl-6 gene was detected in only 1 of these 16 (6%) PMBLS. Point mutations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotting. Missense point mutations of the p53 gene were identified in 3 additional PMBLs (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of Epstein-Barr virus infection were not observed. In conclusion, a variety of molecular lesions occur in PMBLs and may be involved in their pathogenesis. This molecular genetic pattern bears little resemblance to that known for other B cell malignancies, including DLCL. In particular, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs distinguishes them from other DLCLs of B cell origin, suggesting that PMBLs do not represent a distinct subtype of DLCL.

Alternate JournalAm J Pathol
PubMed ID8669486
PubMed Central IDPMC1861633
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Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

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