Molecular characterization of primary mediastinal B cell lymphoma.
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.
Tsang
P
P
Department of Patholoy, Columbia University College of Physicians and Surgeons, New York, USA.
Cesarman
E
E
Chadburn
A
A
Liu
Y F
YF
Knowles
D M
DM
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D016158:Genes, p53 / Q000235:genetics; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D011519:Proto-Oncogenes / Q000235:genetics; D012189:Retrospective Studies