1/4. neurofibromatosis 2 and malignant mesothelioma.Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene cause the inherited disorder NF2 and are also common in malignant mesothelioma, which is not a characteristic feature of NF2. The authors report an asbestos-exposed person with NF2 and malignant mesothelioma. Immunohistochemical analysis of the mesothelioma confirmed loss of expression of the NF2 protein, and comparative genomic hybridization revealed losses of chromosomes 14, 15, and 22, and gain of 7. The authors propose that a person with a constitutional mutation of an NF2 allele is more susceptible to mesothelioma.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/4. Malignant rhabdoid meningioma arising in the setting of preexisting ganglioglioma: a diagnosis supported by fluorescence in situ hybridization. Case report.A highly malignant brain neoplasm with rhabdoid morphological features emerged in the bed of a subtotally resected ganglioglioma in a 54-year-old retired nuclear submarine officer. A combined application of neuroimaging, immunohistochemical studies, electron microscopy, and fluorescence in situ hybridization (FISH) was used to establish the morphological identity of the tumor. The rhabdoid appearance of the tumor cells indicated either an especially malignant variant of rhabdoid meningioma or an atypical teratoid/rhabdoid tumor with an unusually late onset. Whereas immunohistochemical studies and electron microscopy could only be used to narrow down the differential diagnosis, FISH revealed loss of one copy of NF2 with preservation of the INI1 region on 22q, thus establishing the identity of the tumor.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
3/4. Ring chromosome 22 and neurofibromatosis.Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22, mar/46,XY,-22, r(22)/47,XY,-22, r(22) mar/ 47, XY,-22, r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22-specific alphoid repeat probe. dna dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two dna samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor-specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma-associated locus on chromosome 22.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/4. Germline deletion in a neurofibromatosis type 2 kindred inactivates the NF2 gene and a candidate meningioma locus.Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to the development of schwannomas, meningiomas, ependymomas, and juvenile cataracts. The NF2 gene (NF2) has recently been isolated and maps to chromosome 22q12 between the loci D22S212 and D22S32. Deletion studies in sporadic and NF2 associated schwannomas and meningiomas, and the presence of inactivating mutations in NF2 in patients suggest that it acts as a tumor suppressor gene. A candidate meningioma gene (MEN) has also been isolated from the same interval. A new highly polymorphic (CA)n marker, D22S268, which maps very near to NF2, has allowed us to identify a kindred with three living affected individuals, where the disease is presumably caused by a large germline deletion. fluorescence in situ hybridization and pulsed field gel electrophoresis confirm the presence of a 700kb deletion which includes the neurofilament heavy chain subunit gene locus (NEFH), D22S268, NF2 and the putative MEN gene. The absence of meningiomas in this pedigree raises doubts as to the existence of a separate MEN locus in this region. These results support the hypothesis that NF2 results from the inactivation of a tumor suppressor gene on chromosome 22q.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |