A Long Way from Definition of the Molecular Basis to Benefit in the Clinical Management of Ewing Tumours
作者:
H. Kovar,
A. Zoubek,
H. Gadner,
期刊:
Onkologie
(Karger Available online 1996)
卷期:
Volume 19,
issue 3
页码: 234-240
ISSN:0378-584X
年代: 1996
DOI:10.1159/000218804
出版商: S. Karger GmbH
关键词: Ewing’s sarcoma;pPNET;EWS-FLI1;Translocation;Histogenesis;Staging;Disease;localized;Disease;metastatic;RT-PCR screening
数据来源: Karger
摘要:
Recently, the Ewing family of tumours (ET). previously classified by clinical appearance and histology as Ewing’s sarcoma (ES), Askin tumour, peripheral primitive neuroectodermal tumour (pPNET) or neuroepi-thelioma, has been redefined on a purely molecular basis – the presence of specific gene rearrangements. Here, we describe how the recent genetic findings have influenced our view of ET pathophysiology. The t(ll;22), t(21;22), t(7;22) and t(17;22) chromosomal translocations fuse the EWS gene to members of the ETS oncogene family. We present a new functional model for the generation of ET that might explain variable neural marker expression in an otherwise non-neural crest-derived cell by unscheduled gene activation. Currently, two thirds of patients with non-metastatic disease can be cured by multimodal therapy. Patients presenting with metastases, however, have an adverse prognosis which is increasingly corn-batted by myeloablative therapy. Molecular detectability of ET specific aberrations has stimulated great hopes as to the definition of high-risk patients by PCR screening for tumor cells in blood, bone marrow and stem cell phereses. Positive results have been obtained as a consequence of metastatic tumour spread but also due to a large tumour burden or to traumatic or surgical tumour cell mobilisation. Physiological and sampling parameters influence the outcome of the analysis. Thus, the significance of negative/positive results for minimal residual and metastatic disease detection remains to be established. Dissection of the functional cascade in which the aberrant ETS transcription factor is involved might aid in identifying novel biological treatment modalities for the high-risk group of patients. The scope of this review is to describe the potential input of molecular biology on the clinical management of ET as a model tumour and should separate realistic perspectives from utopic dre
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