Molecular heterogeneity of B-lineage diffuse large cell lymphoma.
B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is characterized by a marked degree of clinical heterogeneity. To determine whether or not the clinical heterogeneity of de novo B-DLCL is reflected by heterogeneity in the molecular features of these tumors, we investigated the pattern of distribution of several genetic lesions in 70 cases of de novo B-DLCL at diagnosis. The panel of genetic lesions tested comprised the molecular alterations most frequently detected in B-DLCL, including rearrangements of BCL2, BCL6, and MYC as well as deletions of 6q and mutations of TP53. One or more genetic lesions were detected in 39/70 cases of B-DLCL. Isolated structural alterations of BCL2, BCL6, 6q or TPS3 were detected in 8/70, 10/70, 11/70, and 3/70 cases, respectively. No isolated MYC lesions were detected. Six cases carried different combinations of two genetic lesions, including lesions of BCL2 + BCL6 (1 case), BCL2 + MYC (1 case), BCL2 + 6q (2 cases), or BCL6 + 6q (2 cases). One case had accumulated three genetic lesions, namely a rearrangement of BCL2 and BCL6 and a mutation of TPS3. Overall, these data show that multiple distinct patterns of genetic lesions may associate with de novo B-DLCL, indicating that the molecular pathogenesis of this group of lymphomas is characterized by a high degree of molecular heterogeneity.
Volpe
G
G
Laboratorio di Medicina, Universita di Torina, Italy.
Vitolo
U
U
Carbone
A
A
Pastore
C
C
Bertini
M
M
Botto
B
B
Audisio
E
E
Freilone
R
R
Novero
D
D
Cappia
S
S
De Giuli
P
P
Mazza
U
U
Resegotti
L
L
Palestro
G
G
Saglio
G
G
Gaidano
G
G
D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins / Q000235:genetics; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D016259:Genes, myc; D016158:Genes, p53; D018740:Genetic Heterogeneity; D006566:Herpesviridae Infections / Q000150:complications / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D006801:Humans; D016393:Lymphoma, B-Cell / Q000150:complications / Q000235:genetics* / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000235:genetics* / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors