Lack of topoisomerase copy number changes in patients with de novo and relapsed diffuse large B-cell lymphoma.
Topoisomerase (TOP) gene copy number changes may predict response to treatment with TOP-targeting drugs in cancer treatment. This was first described in patients with breast cancer and is currently being investigated in other malignant diseases. TOP-targeting drugs may induce TOP gene copy number changes at relapse, with possible implications for relapse therapy efficacy. TOP gene alterations in lymphoma are poorly investigated. In this study, TOP1 and TOP2A gene alterations were investigated in patients with de novo diffuse large B-cell lymphoma (DLBCL) (n = 33) and relapsed DLBCL treated with chemotherapy regimens including TOP2-targeting drugs (n = 16). No TOP1 or TOP2A copy number changes were found. Polysomy of chromosomes 20 and 17 was seen in 3 of 25 patients (12%) and 2 of 32 patients (6%) with de novo DLBCL. Among relapsed patients, chromosome polysomy was more frequently observed in 5 of 13 patients (38%) and 4 of 16 patients (25%) harboring chromosome 20 and 17 polysomy, respectively; however, these differences only tended to be significant (p = 0.09 and p = 0.09, respectively). The results suggest that TOP gene copy number changes are very infrequent in DLBCL and not likely induced by TOP2-targeting drugs. Increased polyploidy of chromosomes 17 and 20 among patients with relapsed DLBCL may reflect genetic compensation in the tumor cells after TOP2 inhibition, but is more likely due to the increased genetic instability often seen in progressed cancers. Therefore, it is unlikely that TOP1 and TOP2A gene alterations can be used as predictive markers for response to treatment with TOP2-targeting drugs in patients with DLBCL.
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Mette Ø
MØ
Pedersen
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Tim S
TS
Poulsen
Department of Hematology, Herlev Hospital, Herlev, Denmark.
Anne O
AO
Gang
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Helle
H
Knudsen
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Anne F
AF
Lauritzen
Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
Michael
M
Pedersen
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Signe L
SL
Nielsen
Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
Peter
P
Brown
Department of Pathology, Herlev Hospital, Herlev, Denmark.
Estrid
E
Høgdall
Department of Pathology, Herlev Hospital, Herlev, Denmark. Electronic address: pehno@regionh.dk.
Peter
P
Nørgaard
D000782:Aneuploidy; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D018628:Gene Dosage / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D000069283:Rituximab; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*; D014750:Vincristine / Q000008:administration & dosage
D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D059005:Topoisomerase II Inhibitors; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; D011241:Prednisone