Showing papers by "Robert L. Martuza published in 1987"
TL;DR: The genetic localization of the primary BANF defect strongly supports the concept that the disease locus encodes a 'tumour suppressor' gene, and should provide insights into the pathogenesis of acoustic neuromas and other nervous system tumours.
Abstract: Bilateral acoustic neurofibromatosis (BANF) is a severe autosomal dominant disorder involving development of multiple tumours of the nervous system including meningiomas, gliomas, neurofibromas and particularly bilateral acoustic neuromas. We have used genetic linkage analysis with DNA markers to establish that the defective gene causing BANF is on chromosome 22, and is therefore distinct from the gene for the von Recklinghausen form of neurofibromatosis, which maps to chromosome 17. Linked DNA markers will be particularly valuable in BANF, facilitating early detection of tumours and thereby permitting more effective surgical intervention. In view of the reported loss of genes on chromosome 22 in meningiomas and acoustic neuromas, the genetic localization of the primary BANF defect strongly supports the concept that the disease locus encodes a 'tumour suppressor' gene. Isolation of this gene should provide insights into the pathogenesis of acoustic neuromas and other nervous system tumours, as well as into the control of proliferation and differentiation of neural crest cells.
421 citations
TL;DR: The VRNF gene is genetically linked to the locus encoding nerve growth factor receptor, located on the long arm of chromosome 17 in the region 17q12----17q22, and crossovers with the VRNF locus suggest that a mutation in the nerve growthFactor receptor gene itself is unlikely to be the fundamental defect responsible for the VR NF phenotype.
343 citations
TL;DR: It is proposed that a common mechanism involving chromosome 22 is operative in the development of both tumor types and fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.
Abstract: A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, we propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.
291 citations
TL;DR: Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients, indicating a common pathogenetic mechanism for all three tumor types.
Abstract: Bilateral acoustic neurofibromatosis (BANF) is a genetic defect associated with multiple tumors of neural crest origin. Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients. This indicates a common pathogenetic mechanism for all three tumor types. The two neurofibromas were among three taken from the same patient, and both showed loss of identical alleles demonstrating that the same chromosome suffered deletion in both tumors. The third neurofibroma from this patient showed no detectable loss of heterozygosity, which suggests the possibility of a more subtle mutational event that affects chromosome 22. In the two acoustic neuromas, only a portion of chromosome 22 was deleted, narrowing the possible chromosomal location of the gene that causes BANF to the region distal to the D22S9 locus in band 22q11. The identification of progressively smaller deletions on chromosome 22 in these tumor types may well provide a means to clone and characterize the defect.
234 citations
TL;DR: The surgical results in 69 patients with unilateral tumors of the cerebellopontine angle or internal auditory canal in whom total tumor removal was accomplished, and in whom an attempt was made to preserve hearing, suggest that the success rate of preservation of hearing and facial nerve function was correlated with the size of the tumor.
Abstract: The surgical results in 69 patients with unilateral tumors of the cerebellopontine angle or internal auditory canal in whom total tumor removal was accomplished, and in whom an attempt was made to preserve hearing, are presented. The success rate of preservation of hearing and facial nerve function was correlated with the size of the tumor. Useful hearing, as defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%, was preserved in 73% of cases in which the tumor extension to the posterior fossa was no greater than 0.5 cm. In contrast, useful hearing was preserved in 22% of cases in which posterior fossa extension was greater than 2.5 cm. No significant correlation was found between preoperative evoked responses and success in preservation of hearing. The techniques and value of intraoperative monitoring of electrocochleogram (ECoG) and brain stem evoked responses are discussed. A theory of pathogenesis of intraoperative hearing loss, based on correlation of changes in evoked responses and simultaneous surgical events, is presented.
124 citations
TL;DR: Linkage analysis with the human oncogene homolog erbA1, which maps to this region, suggests that this cancer-related gene is not the primary cause of NF1, and a preliminary multipoint linkage analysis suggests that the NF1 gene is located on the long arm of chroomsome 17.
24 citations
TL;DR: Different molecular-genetic approaches towards identifying and characterization of the NF genes, based on their chromosomal localizations, will have profound implications for diagnosis and treatment of these diseases and might yield significant insights into mechanisms controlling development and differentiation of the human nervous system.
Abstract: Neurofibromatosis (NF) is one of the most frequent and clinically important Mendelian disorders in man, with an incidence of 1 in 3,000. While different organ systems and cell types can be affected in
5 citations