title: Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.
abstract: Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.
authors.affiliation: UOA Ematologia, Dipartimento di Oncologia, Azienda Ospedaliera S Giovanni Battista, Torino, Italy. uvitolo@molinette.piemonte.it
authors.forename: U
authors.initials: U
authors.lastname: Vitolo
authors.forename: B
authors.initials: B
authors.lastname: Botto
authors.forename: D
authors.initials: D
authors.lastname: Capello
authors.forename: D
authors.initials: D
authors.lastname: Vivenza
authors.forename: V
authors.initials: V
authors.lastname: Zagonel
authors.forename: A
authors.initials: A
authors.lastname: Gloghini
authors.forename: D
authors.initials: D
authors.lastname: Novero
authors.forename: G
authors.initials: G
authors.lastname: Parvis
authors.forename: R
authors.initials: R
authors.lastname: Calvi
authors.forename: C
authors.initials: C
authors.lastname: Ariatti
authors.forename: I
authors.initials: I
authors.lastname: Milan
authors.forename: M
authors.initials: M
authors.lastname: Bertini
authors.forename: C
authors.initials: C
authors.lastname: Boccomini
authors.forename: R
authors.initials: R
authors.lastname: Freilone
authors.forename: P
authors.initials: P
authors.lastname: Pregno
authors.forename: L
authors.initials: L
authors.lastname: Orsucci
authors.forename: G
authors.initials: G
authors.lastname: Palestro
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D015993:Life Tables; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D017354:Point Mutation; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D008558:Melphalan; D002330:Carmustine; D011241:Prednisone; D008727:Methotrexate