Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell l
ymphoma (DLCL) postulated to arise from noncirculating thymic B lympho
cytes, Because of its distinctive clinical and morphological features
and putative unique cellular origin, PMBL is generally considered a di
stinct clinicopathological entity. Little is known, however, about the
molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs fo
r molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ra
s, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, w
hich are commonly involved in lymphoid neoplasia. Employing a combinat
ion of Southern blotting and/or polymerase chain reaction and single-s
trand conformation polymorphism assays, we detected genetic alteration
s 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 on
ly 1 of these 16 (6%) PMBLs. Point mutations of the 5' noncoding regio
n of the c-myc gene were demonstrated in 3 other cases (19%), although
c-myc gene rearrangements were not seen by Southern blotting. Missens
e point mutations of the p53 gene were identified in 3 additional PMBL
s (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of
Epstein-Barr virus infection were not observed. In conclusion, a vari
ety of molecular lesions occur is PMBLs and may be involved in their p
athogenesis. This molecular genetic pattern bears little resemblance t
o that known for other B cell malignancies, including DLCL. In particu
lar, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs di
stinguishes them from other DLCLs of B cell origin, suggesting that PM
BLs do represent a distinct subtype of DLCL.