21 research outputs found
INI1 mutations in meningiomas at a potential hotspot in exon 9
Rhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized. Our data indicate that the INI1 is a second tumour suppressor gene on chromosome 22 that may be important for the genesis of meningiomas. © 2001 Cancer Research Campaign http://www.bjcancer.co
Furomegistines I and II, two furanopyridine alkaloids from the bark of Sarcomelicope megistophylla
Two alkaloids, furomegistine I (1) and furomegistine II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data. Both belong to the category of furanopyridine alkaloids and should be considered as oxidation products of a furo[2,3-b]quinoline precursor. The two alkaloids exhibited moderate cytotoxic activity. © 2001 Elsevier Science Ltd
The structure of sarcomejine: An application of long-range 1H-15N correlation at natural abundance
A new 4(1H)-quinolinone alkaloid, sarcomejine (1), has been isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data and especially with a long-range 1H-15N correlation NMR spectrum at natural abundance
Megistolactone, a new alkaloid from Sarcomelicope megistophylla
A new quinolone alkaloid, megistolactone (1) was isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data. From a biogenetic point of view, this compound should be considered as an oxidation product of 1,2,3,4-tetra-O-subsituted acridone alkaloids, which are also present in the bark
Two new alkaloids from the bark of Sarcomelicope megistophylla
Two new alkaloids, megistophylline I (1) and megistophylline II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data
Koniamborine, the first pyrano[3,2-b]indole alkaloid and other secondary metabolites from Boronella koniambiensis
Two new alkaloids, (-)-cis-1,2-dihydroxy-1,2-dihydromedicosmine (3) and koniamborine (4), have been isolated from Boronella koniambiensis aerial parts. Their structures have been established from NMR and mass data. Koniamborine is a novel type of alkaloid, which derives from the pyrano[3,2-6]indole basic skeleton, described for the first time from nature. 6-Methoxy-1-methylisatin, also present in the plant material, can be considered biogenetically as a degradation product of the fused pyrone ring of 4. © 2005 American Chemical Society and American Society of Pharmacognosy
Wilms’ tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas
Nephroblastoma (Wilms’ tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities
predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15
region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith–Wiedemann, Simpson–Golabi–Behmel and Perlman
syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three
unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth
syndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 gene.
Subsequently, we identified a somatic PTCH1 nonsense mutation in the renal tumor of one patient. In addition, by array
comparative genomic hybridization method, we analyzed the DNA extracted from the blood samples of nine patients with
overgrowth syndrome and WT, but did not identify any deleterious chromosomal imbalances in these patients. These findings
strongly suggest that patients with constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1 have a
role in the pathogenesis of nephroblastomas