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Deletion of genes on chromosome 1 in endocrine neoplasia
Abstract:
Recent studies have identified normal cellular DNA sequences which are lost in the development of embryonal and adult tumours. These tumours are thought to arise after a primary mutation in one allele of such a sequence is followed by loss of its normal homologue. In familial cases, the primary mutation is transmitted in the germ line. The secondary mutation may involve a substantial loss of chromosomal material and thus lead to identification of the site of the inherited mutation. We have examined constitutional and tumour genotypes of medullary thyroid carcinomas and phaeochromocytomas which develop in the dominantly inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2) to locate the predisposing gene in this syndrome. We observed deletion of a hypervariable region of DNA on the short arm of chromosome 1 in seven out of fourteen tumours. Analysis of the parental origin of the deleted allele in two families showed that it was derived from the affected parent in one case, which suggests that the deletion does not reflect the site of the inherited mutation in MEN2. The deleted region is distal to the breakpoint commonly detected in neuroblastomas, which share with the tumours of MEN2 embryological origin from neuroectoderm.
Insights
Researchers investigated genetic deletions in Multiple Endocrine Neoplasia type 2 (MEN2) tumors. They found DNA deletions on chromosome 1 in half of the tumors analyzed, suggesting a role in MEN2 tumor development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Tumorigenesis involves the loss of normal cellular DNA sequences.
- Familial cancer syndromes often result from inherited mutations followed by loss of the normal gene copy.
- Multiple Endocrine Neoplasia type 2 (MEN2) is an inherited cancer syndrome.
Purpose of the Study:
- To locate the predisposing gene for Multiple Endocrine Neoplasia type 2 (MEN2).
- To investigate constitutional and tumor genotypes in MEN2 patients with medullary thyroid carcinomas and phaeochromocytomas.
Main Methods:
- Genotyping of constitutional DNA and tumor DNA from MEN2 patients.
- Analysis of DNA deletions, specifically in a hypervariable region on chromosome 1 short arm.
- Parental origin analysis of deleted alleles in familial cases.
Main Results:
- Deletion of a hypervariable DNA region on chromosome 1 short arm was observed in 7 out of 14 MEN2 tumors.
- Parental origin analysis indicated the deletion was not consistently linked to the inherited mutation site in MEN2.
- The deleted region was found to be distal to the breakpoint common in neuroblastomas.
Conclusions:
- The observed DNA deletions on chromosome 1 may be associated with MEN2 tumor development.
- The deletions do not appear to directly represent the inherited mutation site in MEN2.
- Further research is needed to pinpoint the exact predisposing gene in MEN2.