High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has be...

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Bibliographic Details
Published in:British journal of cancer 2013-12, Vol.109 (12), p.3084-3091
Main Authors: Bonvini, P, Zin, A, Alaggio, R, Pawel, B, Bisogno, G, Rosolen, A
Format: Article
Language:English
Subjects:
692/699/67/1798
692/700/1720
692/700/1750
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Cell cycle
Cell Line, Tumor
Child
Diseases of the osteoarticular system
Drug Resistance
Epidemiology
Female
Gene Expression
Hematology
Histology
Humans
Immunohistochemistry
Kinases
Lymphoma
Male
Medical prognosis
Medical research
Medical sciences
Molecular Diagnostics
Molecular Medicine
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Oncology
Pediatrics
Phosphorylation
Prognosis
Proteins
Receptor Protein-Tyrosine Kinases - biosynthesis
Receptor Protein-Tyrosine Kinases - genetics
Rhabdomyosarcoma - enzymology
Rhabdomyosarcoma - genetics
Rhabdomyosarcoma - pathology
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Survival Analysis
Tumors
Tumors of striated muscle and skeleton
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Summary:Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clinical impact on patients’ stratification and outcome. Methods: Specimens were obtained from RMS patients and cell lines, and ALK expression was analysed by quantitative RT–PCR, western blotting, IHC, and copy number analysis. Results: High ALK mRNA expression was detected in the vast majority of PAX3/7-FOXO1-positive tumours, whereas PAX3/7-FOXO1-negative RMS displayed considerably lower amounts of both mRNA and protein. Notably, ALK mRNA distinguished unfavourable PAX3/7-FOXO1-positive tumours from PAX3/7-FOXO1-negative RMS ( P
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2013.653