Cyclin D1, a novel molecular marker of minimal residual disease, in metastatic neuroblastoma.
Accurate monitoring of minimal residual disease (MRD) is critical for the management of metastatic neuroblastoma (NB). We evaluated cyclin D1 (CCND1), a cell-cycle control gene, as a novel MRD marker of NB. Using quantitative reverse transcriptase-polymerase chain reaction, we studied CCND1 expression in 133 solid tumors of different histological types, including 39 NB tumors, and examined its potential clinical utility as an early response marker in the bone marrows before and after treatment of 118 stage 4 patients enrolled after induction chemotherapy in an immunotherapy protocol. Based on 40 normal marrow and peripheral blood samples, a CCND1 transcript value greater than the mean + 2 SD was defined as positive. Sensitivity of this assay was one NB cell in 10(6) normal mononuclear cells. CCND1 transcript levels were high in NB, breast cancer, and Ewing family tumors. Among the NB patients evaluated, early (2.5 months from protocol entry) marrow response was strongly associated with both progression-free (P=0.0001) and overall survival (P=0.0006). CCND1 response remained predictive of survival among a subset of 66 patients who had no histological evidence of marrow disease before immunotherapy. We conclude that CCND1 has potential clinical utility as a novel molecular marker of MRD in the bone marrow of patients with metastatic NB.
Cheung
Irene Y
IY
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA. cheungi@mskcc.org
Feng
Yi
Y
Vickers
Andrew
A
Gerald
William
W
Cheung
Nai-Kong V
NK
D014408:Biomarkers, Tumor / Q000235:genetics*; D001853:Bone Marrow; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019938:Cyclin D1