Regression and progression in neuroblastoma. Does genetics predict tumour behaviour?

doi:10.1016/0959-8049(95)00044-J

European Journal of Cancer

Volume 31, Issue 4, 1995, Pages 510-515

https://doi.org/10.1016/0959-8049(95)00044-J Get rights and content

Abstract

Neuroblastoma (NB) is a heterogeneous disease. The clinical course may range from spontaneous regression and maturation to very aggressive behaviour. Stage 4s is a unique subcategory of NB, generally associated with good prognosis, despite skin and/or liver involvement and the frequent presence of tumour cells in the bone marrow. Another type of NB is the locally invasive tumour without bone and bone marrow involvement which can also have a good prognosis, irrespective of lymph node involvement. Unfortunately, there is only limited biological information on such tumours which have not been treated with cytotoxic therapy despite lymph node involvement, residual tumour mass after surgery and/or bone marrow infiltration. In order to find specific genetic changes common to NBs with a benign clinical course, we studied the genetic abnormalities of these tumours and compared them with highly aggressive tumours. We analysed a series of 54 localised and stage 4s tumours by means of in situ hybridisation performed on fresh cells or on paraffin embedded tissues. In addition, we performed classical cytogenetics, Southern blotting and PCR analysis on fresh tumour tissue. The majority of patients had been treated with surgery alone, and in a number of patients tumour resection was incomplete. Deletions at 1p36 and amplifications of the MYCN oncogene were absent, and diploidy or tetraploidy were not seen in any case, with residual localised tumours possessing a favourable outcome. Unexpectedly, one patient with a tetraploid 4s tumour without any genetic structural changes not receiving any cytotoxic treatment, did well. Interestingly, this genetic spectrum contrasted with that of progressing tumours, in which most had genetic aberrations, the deletion at 1p36 being the most common event. These data, although limited, suggest that an intact 1p36 (recognised by D1Z2), the absence of MYCN amplification and near-triploidy (at least in localised tumours), represent prerequisites for spontaneous regression and/or maturation.

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Some patients may experience spontaneous regression or differentiation into benign ganglioneuroma, while others still have a poor prognosis even after adopting intensive treatment strategies [8–10]. In the low-risk group, spontaneous regression, differentiation, and good response to surgery and chemotherapy are often shown [11]. However, among children older than 18 months, the efficacy of intensive chemotherapy and stem cell transplantation is reduced [12].
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The clinical spectrum can range from spontaneous regression and maturation to aggressive dissemination despite multimodal therapy. Molecular genetics have been used to characterize and define clinically relevant subgroups of neuroblastoma [1–3], and several genetic alterations correlate with outcome and response to therapy (e.g., 1p loss, 17q gain, MYCN amplification, etc.) [4–7]. Recent genome-wide analysis has identified novel regions of frequent allelic imbalance in neuroblastoma that may also be associated with distinct clinical subgroups [8].
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PaperRegression and progression in neuroblastoma. Does genetics predict tumour behaviour?

Abstract

Cancer Genet. Cytogenet

Lancet

Cytogenetic features of human neuroblastomas and cell lines

Cancer Res

Different karyotypic patterns in early and advanced stage neuroblastoma

Cancer Res

Tumour karyotype discrimatesbetween good and bad prognostic outcome in neuroblastoma

Br J Cancer

Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1

Cancer

Clinical relevance of tumour cell ploidy and N-myc gene amplification in childhood neuroblastoma: a pediatric oncology group study

J Clin Oncol

Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc

Nature

Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastoma: correlation with N-myc amplification

Molecular basis of clinical heterogeneity in neuroblastoma

Am J Ped Hematol/Oncol

Excellent outcome of stage II neuroblastoma is independent of residual disease and radiation therapy

J Clin Oncol

Stage II neuroblastoma: adverse prognostic significance of lymph node involvement

Arch Dis Child

Proof of the reactive nature of the Schwann cell in neuroblastoma and its clinical implications

A proposed staging for children with neuroblastoma

Cancer

A review of 17 IV-S neuroblastoma patients at the children's hospital of Philadelphia

Cancer

Complete pathologic maturation and regression of stage IV-S neuroblastoma without treatment

Cancer

Paper
Regression and progression in neuroblastoma. Does genetics predict tumour behaviour?