mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis
| Autor: | Ingrid Øra, Anita Kullman, Åsa Vernby, Per Kogner, Catarina Träger, Bertil Kågedal |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Carboxy-lyases Adolescent Tyrosine 3-Monooxygenase Biology Risk Assessment Sensitivity and Specificity Gene Expression Regulation Enzymologic Neuroblastoma Bone Marrow Predictive Value of Tests Risk Factors Internal medicine Cell Line Tumor medicine Biomarkers Tumor Humans Child Neoplasm Staging Sweden Aromatic L-amino acid decarboxylase Messenger RNA Tyrosine hydroxylase Reverse Transcriptase Polymerase Chain Reaction Infant Newborn Cancer Infant Reproducibility of Results medicine.disease Prognosis Minimal residual disease Gene Expression Regulation Neoplastic medicine.anatomical_structure Endocrinology Treatment Outcome Oncology Case-Control Studies Child Preschool Dopa Decarboxylase N-Acetylgalactosaminyltransferases Female Bone marrow |
| Zdroj: | International journal of cancer. 123(12) |
| ISSN: | 1097-0215 |
| Popis: | Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of children with localized neuroblastoma with increased results in PB did not differ between the three transcripts. In these children, all without morphologically detectable neuroblastoma in BM, the number of patients with elevated GD2S in BM at diagnosis was significantly higher than for the other transcripts (10/16 elevated, p = 0.012). GD2S was elevated in PB from 10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p < 0.001). In BM from these children GD2S was significantly elevated. We conclude that high expression of TH and DDC both in PB and BM corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome. Children with high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma detection in PB and BM. |
| Databáze: | OpenAIRE |
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