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Alternative splicing of the neural cell adhesion molecule and the differential diagnosis of neuroblastoma

Phimister, Elizabeth Giorsal; (1993) Alternative splicing of the neural cell adhesion molecule and the differential diagnosis of neuroblastoma. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

While the survival rate of children diagnosed with cancer has more than doubled in the last 25 years, neuroblastoma, accounting for 7–9% of all childhood malignancies, remains a disease with a poor prognosis. In some cases, confusion between neuroblastoma and other "small round cell" tumours, such as rhabdomyosarcoma, contributes to erroneous diagnosis and inappropriate treatment. This thesis addresses the possibility of distinguishing such tumours by differential expression of the neural cell adhesion molecule (NCAM). Fluorescence-activated flow cytometry revealed expression of NCAM by 6/7 neuroblastoma cell lines tested. Western blotting showed that underlying a uniform sialylation, a heterogeneity of isoform expression exists although neuroblastoma and rhabdomyosarcoma cell lines could not be distinguished by isoform complement. Analyses of two alternative splicing regions in the extracellular domain suggest that tissue-specific variations of NCAM may exist. Splicing patterns at both of these regions were examined in neuroblastoma and rhabdomyosarcoma cell lines by amplifying cDNA complementary to cellular RNA, using the polymerase chain reaction. Products were analysed by Southern blotting and sequence analysis. The Variable Alternatively-Spliced Exon (VASE), previously thought to be restricted to tissues of the nervous system, was found in all rhabdomyosarcoma cell lines tested. However, its presence in all neuroblastoma cell lines examined, renders it a poor candidate by which to differentiate the two cell types. The sequence of human VASE was determined. Evidence suggests that three of the four alternatively-spliced exons constituting the "muscle-specific" domain (MSD1) are spliced into RNA synthesised by some neuroblastoma cell lines. The expression of components of the MSD1 domain may provide a basis on which neuroblastoma and rhabdomyosarcoma may be distinguished; MSD1c was found in NCAM of rhabdomyosarcoma cell lines but not that of neuroblastoma cell lines. These findings indicate that NCAM expression is more complex than first assumed, and that a detailed study of the expression of NCAM on the "small round cell" tumours can lead to a highly selective approach in designing reagents for distinguishing the two types of tumours analysed here.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Alternative splicing of the neural cell adhesion molecule and the differential diagnosis of neuroblastoma
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Neural cell adhesion; Neuroblastoma
URI: https://discovery.ucl.ac.uk/id/eprint/10103736
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