Amyloid deposits were found in one solitary tumour and in the tumour from the MEN-I patient, both staining strongly positive with anti-IAPP antibodies; cytoplasmatic IAPP was weak.
We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb).
We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb).
We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb).
Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1).
Extensive experience from patients with gastrinoma as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome has revealed that MEN 1-gastrinoma patients show important differences from patients with sporadic gastrinoma.
PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.
Our localization of the human protooncogene SEA between PYGM and INT2, two markers that flank MEN-1, suggests SEA as a potential candidate for the MEN-1 locus.
Our localization of the human protooncogene SEA between PYGM and INT2, two markers that flank MEN-1, suggests SEA as a potential candidate for the MEN-1 locus.
PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.
PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.
PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.
Our localization of the human protooncogene SEA between PYGM and INT2, two markers that flank MEN-1, suggests SEA as a potential candidate for the MEN-1 locus.
Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked.
On the basis of the finding of a basic fibroblast growth factor (bFGF)-like substance circulating in plasma of MEN1 patients, we chose a bFGF-related gene known to be localized to 11q13 as one of the markers.
The causative medical treatment of patients with malignant endocrine pancreatic tumors and the MEN-1 trait include chemotherapy (streptozotocin plus 5-fluorouracil), interferons and the somatostatin analogue SMS 201-995.
We conclude that many "hyperplastic" parathyroid tumors in familial MEN-1 are in fact monoclonal and may progress or even begin to develop by inactivation of the MEN-1 gene (at 11q13) in a precursor cell.
We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15).