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Absence of MEN2A- or 2B-type RET mutations in primary neuroblastoma tumour tissue
A E Peaston1, M L Camacho, M D Norris
1Children's Cancer Institute Australia, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Abstract:
Specific germline mutations in the RET proto-oncogene predispose to the familial cancer syndromes: multiple endocrine neoplasia (MEN) types 2A and 2B, and familial medullary thyroid carcinoma. Expression of the RET receptor tyrosine kinase is tightly restricted to tumours of neural crest origin, such as neuroblastoma, and neuroblastoma has been observed in RET transgenic mice. Neuroblastoma tumour cell lines transfected with the MEN2A RET gene exhibit spontaneous neuritic differentiation, whereas MEN2B-type RET transfectants demonstrate altered cell adhesion and enhanced metastatic potential. In this study, the authors examined genomic DNA from 26 primary neuroblastoma tumours for MEN2A and MEN2B RET mutations, using restriction enzyme digestion of polymerase chain reaction products as an alternative to direct sequencing. Examination of RET exons 10 (codons 611, 618, 620), 11 (codons 632, 633, 634) and 16 (codon 918) in all 26 tumours revealed no RET mutations. Taken together these data suggest that abnormalities of the RET signalling pathway, rather than oncogenic, MEN2-type RET activation by mutation, may play a role in neuroblastoma tumorigenesis.
Insights
This study investigated RET proto-oncogene mutations in neuroblastoma, finding no specific MEN2A or MEN2B mutations. These findings suggest RET signaling pathway abnormalities, not direct mutations, may drive neuroblastoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Germline mutations in the RET proto-oncogene are linked to familial cancer syndromes like MEN2A and MEN2B.
- RET receptor tyrosine kinase expression is specific to neural crest tumors, including neuroblastoma.
- Previous studies show RET gene transfection influences neuroblastoma cell differentiation and metastasis.
Purpose of the Study:
- To investigate the presence of MEN2A and MEN2B RET mutations in primary neuroblastoma tumors.
- To explore the role of RET proto-oncogene mutations in neuroblastoma tumorigenesis.
Main Methods:
- Genomic DNA from 26 primary neuroblastoma tumors was analyzed.
- Polymerase chain reaction (PCR) and restriction enzyme digestion were used to detect RET mutations.
- Specific RET exons (10, 11, and 16) were examined for mutations.
Main Results:
- No MEN2A or MEN2B RET mutations were detected in any of the 26 primary neuroblastoma tumors.
- Analysis of RET exons 10, 11, and 16 did not reveal specific pathogenic mutations.
Conclusions:
- The study did not find evidence of oncogenic RET mutations (MEN2-type) in the analyzed neuroblastoma cohort.
- Abnormalities within the RET signaling pathway, rather than direct RET gene mutations, may contribute to neuroblastoma development.
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