Genomic lesions associated with a different clinical outcome in diffuse large B-Cell lymphoma treated with R-CHOP-21.
Despite recent therapeutic improvements, the clinical course of diffuse large B-cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi-centre study to evaluate the impact of genomic aberrations detected using a high-density genome wide-single nucleotide polymorphism-based array on clinical outcome in a population of DLBCL patients treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R-CHOP-21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R-CHOP, have been identified by arrayCGH.
Scandurra
Marta
M
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Mian
Michael
M
Greiner
Timothy C
TC
Rancoita
Paola M V
PM
De Campos
Cassio P
CP
Chan
Wing C
WC
Vose
Julie M
JM
Chigrinova
Ekaterina
E
Inghirami
Giorgio
G
Chiappella
Annalisa
A
Baldini
Luca
L
Ponzoni
Maurilio
M
Ferreri
Andres J M
AJ
Franceschetti
Silvia
S
Gaidano
Gianluca
G
Montes-Moreno
Santiago
S
Piris
Miguel A
MA
Facchetti
Fabio
F
Tucci
Alessandra
A
Nomdedeu
Josep Fr
JF
Lazure
Thierry
T
Lambotte
Olivier
O
Uccella
Silvia
S
Pinotti
Graziella
G
Pruneri
Giancarlo
G
Martinelli
Giovanni
G
Young
Ken H
KH
Tibiletti
Maria Grazia
MG
Rinaldi
Andrea
A
Zucca
Emanuele
E
Kwee
Ivo
I
Bertoni
Francesco
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone