PubMed Health⌕ Search

Biomedical subjects

M J Bello

Publications and source records attributed to M J Bello.

At least 19 recordsLinked to original sources
PubMed1998

Six novel mutations in the NF2 tumor suppressor gene.

Six novel mutations were identified in the NF2 tumor suppressor gene in a panel of meningiomas and neurinomas. Screening was performed using a combination of single-strand conformation polymorphism and heteroduplex analyses on polymerase chain reaction-amplified DNA from tumors and matched peripheral blood lymphocytes. Mutations involved exons 2, 7, 11 and 12, and corresponded to three frameshift, one nonsense, one missense and one polymorphism.

Chromosome Aberrations↗
PubMed1995

Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors.

The molecular mechanisms underlying the genesis and progression of oligodendroglial tumors are poorly understood, since only restricted information on loss of heterozygosity from isolated cases is available. The commonest alterations appear to involve deletion of 1p and 19q, while loss of heterozygosity for 9p, chromosome 10 or epidermal growth factor receptor gene amplification have been described in single tumors. We have applied restriction fragment length polymorphism analysis to 14 loci covering chromosome 1 and 7 loci on chromosome 19 in a series of 25 tumors with an oligodendroglial component to determine precisely the participation of these suppressor genes in the genesis of tumors. Twenty-two and 19 of the 25 samples displayed LOH at 1p and 19q, respectively, and both anomalies were detected in association in 17 samples, including low- and high-grade oligodendrogliomas as well as mixed oligo-astrocytomas. Our findings suggest that inactivation of tumor suppressor genes located on 1p and 19q represent cooperative alterations occurring at early stages of oncogenic transformation of oligodendroglial neoplasms.

Chromosome Deletion↗
PubMed1995

Allelic status of chromosome 1 in neoplasms of the nervous system.

By using five highly polymorphic markers, the allelic status of chromosome 1 was established in a series of 236 tumors of the nervous system, including all major histologic subtypes: gliomas, meningiomas, neurinomas, neuroblastomas, medulloblastomas, etc. Loss of alleles at 1p was observed at significant frequencies in neuroblastomas (26% of cases), meningiomas (32%), and malignant gliomas (37%) (primarily oligodendrogliomas [94%]). This anomaly was also detected in two of 23 neurinomas, two of three neurofibrosarcomas, one primary lymphoma, and two metastatic tumors of the brain. The analysis of tumors displaying partial 1p deletions suggests the existence of two distinct regions, 1p36 and 1p35-p32, in which loci nonrandomly involved in the development of neurogenic neoplasms might be located.

Alleles↗
PubMed1995

Thyroid function surveillance in CAPD patients.

We monitored thyroid function in 75 peritoneal dialysis patients (55 +/- 15 years). A total of 20 (27%) were hypothyroid; 9 were diagnosed about the time of initiation of dialysis, and 11 prior to onset of renal failure. Thyroid function surveillance found an increase in serum thyrotropin (TSH) concentration to hypothyroid values in only one patient. On replacement therapy serum thyroxine was similar in euthyroid and hypothyroid patients (6.94 +/- 1.69 vs 6.52 +/- 1.65 micrograms/dL, respectively; p = 0.380), but TSH was higher in hypothyroid patients (5.61 +/- 5.67 vs 2.59 +/- 1.49 microU/mL, respectively; p = 0.001). Serum creatinine (8.6 +/- 3.1 vs 11.4 +/- 5.1 mg/dL, respectively; p = 0.049) and albumin concentrations (3.76 +/- 0.47 vs 3.33 +/- 0.71 g/dL, respectively; p = 0.006) were lower in hypothyroid than euthyroid patients. Hyperthyroid patients had higher serum triglyceride concentrations than euthyroid patients (306 +/- 176 vs 189 +/- 122 mg/dL, respectively; p = 0.013). Parathyroid hormone (PTH) was lower in hypothyroid than normothyroid patients (108 +/- 80 vs 261 +/- 265 pg/mL, respectively; p = 0.032). No differences were observed in serum calcium, phosphorus, and alkaline phosphatase. We conclude that hypothyroidism is common in peritoneal dialysis patients, usually antedates dialysis therapy, results in lower serum albumin and creatinine concentrations and higher serum triglyceride concentrations, is associated with lower serum PTH concentrations, and that thyroid function surveillance is not necessary in the absence of symptoms suggestive of hypothyroidism.

Alkaline Phosphatase↗
PubMed1995

[Neurologic diseases due to alterations in oncogenes and tumor suppressing genes].

Tumor growth is a dynamic combination of cell changes that confer a selective advantage for growth in vivo, implying the deregulation of processes that control cell proliferation along with the genesis of increasingly aggressive tumoral forms capable of invasion and metastasis. Such highly malignant tumors are the result of several alterations in genetic material, particularly in 2 types of genes: oncogenes and tumor suppressant genes that involve the activation and loss, respectively, of cell growth regulatory functions. Neurogenic tumors present either in the context of familial syndromes that predispose to cancer or sporadically, in individuals with no previous family history of neoplasia. The identification and description of some of the genes responsible for these syndromes has demonstrated that they generally are tumor suppressors that also participate actively in the genesis of sporadic forms of the same histological classes of tumor. We summarize recently acquired molecular understanding of syndromes that predispose to the development of neural tumors and review the available data on the sequence of molecular changes that contribute to neoplastic transformation and tumor progression toward aggressive forms in gliomas and meningiomas.

Brain↗
PubMed1994

Molecular analysis of chromosome 1 abnormalities in human gliomas reveals frequent loss of 1p in oligodendroglial tumors.

Alterations of the short arm of chromosome 1 are recurrently found in cytogenetic analysis of malignant gliomas, and deletions of 1p36-p32 region characterize at least the higher-grade tumors, glioblastoma multiforme. Molecular analysis of tumor-derived and normal genomic DNA from 57 cases of gliomas, using a panel of chromosome 1-specific DNA probes showed LOH in 16 tumors. Allelic losses on 1p were primarily restricted to glioblastoma multiforme (2/11) and to tumors with a major oligodendroglial component: grade II oligodendrogliomas (6/6), grade III anaplastic oligodendrogliomas (5/6) and grade II-III mixed oligo-astrocytomas (2/3). Losses for 1q markers were detected in only 1 tumor (glioblastoma multiforme). Our data suggest that anomalies of 1p primarily characterize oligodendrogliomas, whereas they are rare events in astrocytic tumors and indicate that a tumor-suppressor gene on 1p36-p32 is involved in the development of brain tumors with oligodendroglial differentiation.

Alleles↗
PubMed1994

Molecular and cytogenetic analysis of chromosome 9 deletions in 75 malignant gliomas.

A deletion mapping analysis of chromosome 9 has been performed on a series of 75 samples derived from malignant gliomas. A total of 27 tumors displayed different deletions for the loci studied (D9S1, NRASLI, D9S18, IFNA, and IFNBI). In most instances, losses involving the markers located on the short arm of chromosome 9 were observed, and only two samples were characterized by losses of the short and long arms. Either partial or complete homozygous deletions of IFN genes were observed in 15 cases, and 12 other samples showed hemizygous deletions for these genes. The results show that the 9p abnormalities are not exclusive to high-grade astrocytic tumors, as some low-grade samples (two astrocytoma grade II and six oligodendrogliomas) displayed this anomaly which, in a few instances, was the sole abnormality detected.

Chromosome Deletion↗
PubMed1994

Allelic loss at 1p is associated with tumor progression of meningiomas.

Next to chromosome 22 anomalies, deletions of the short arm of chromosome 1 have previously been described as the most frequent alteration detected by cytogenetic analysis of meningiomas. To determine the incidence of these deletions, we have analyzed a series of 50 meningiomas for the loss of alleles at four chromosome 1 loci. Thirteen samples displayed LOH for the markers studied; in one instance, the results were compatible with loss of the entire chromosome 1, whereas in the other 12 samples deletions of the short arm were observed. Eleven of the meningiomas had previously been shown to have loss of alleles on chromosome 22, and 12 of them were characterized by increased tumor aggressiveness. These findings suggest that deletion of Ip (or the alteration of a locus located there) might represent a secondary, but nonrandom alteration in meningiomas, perhaps contributing to meningioma tumor progression.

Alleles↗
PubMed1994

No TP53 mutations in neuroblastomas detected by PCR-SSCP analysis.

We have analysed 29 neuroblastomas for TP53 mutations in exons 5 to 8 by means of the polymerase chain reaction in combination with the single-strand conformation polymorphism technique. We could not detect any mutation. These results indicate that, in contrast to the majority of tumors so far studied, TP53 mutations do not seem to be important for the development of neuroblastomas.

DNA, Neoplasm↗
PubMed1994

Ascertainment of chromosome 7 gains in malignant gliomas by cytogenetic and RFLP analyses.

The incidence of gains involving chromosome 7 was determined independently using cytogenetic and molecular genetic analyses in a series of 57 malignant gliomas. Coincidental results were observed in the group of tumors in which trisomy 7 was identified on the same cells that also displayed other clonal abnormalities (i.e., losses of chromosome 10, and structural rearrangements of 1p, 9p, etc., and the presence of dmin). On the other hand, molecular detection of gain of material from this chromosome was obtained in only one of nine cases in which trisomy 7 had been identified as a solitary anomaly at the cytogenetic level. Thus, although trisomy 7 has been identified as a clonal abnormality in about 60% of gliomas analyzed cytogenetically so far, our findings suggest that the anomaly may be representative of tumor parenchyma in half of them, while in the remaining cases (mainly those in which trisomy 7 is observed at the cytogenetic level as the sole chromosomal deviation) our data agree with those suggesting that the anomaly is the result of an in vitro non-disjunction, or represent in vivo mosaicism of the non-tumoral cells.

Blotting, Southern↗
PubMed1994

Molecular analysis of genomic abnormalities in human gliomas.

A series of 57 malignant gliomas, including 27 astrocytomas grade III-IV (glioblastoma multiforme), 15 astrocytomas grade I-II, and 15 tumors with major oligodendroglial component, was examined to detect molecular abnormalities of loci at specific chromosome regions. At the cytogenetic level, these regions have been shown to be nonrandomly involved in neoplastic development of these histologic subtypes of tumor. We used a panel of 24 polymorphic DNA probes to analyze loss of heterozygosity (LOH) at loci on chromosomes 7, 9, 10, 13, 17p, and 22q. In addition, the retinoblastoma (RB1) oncosuppressor gene, the platelet-derived growth factor A (PDGFA) gene, and the epidermal growth factor receptor (EGFR) gene were analyzed directly. Loss of genetic information on the short arm of chromosome 17 was observed in both low- and high-grade astrocytomas, whereas no oligodendroglial tumor was characterized by this type of aberration. LOH for chromosome 10, mainly compatible with loss of the entire chromosome, was primarily evidenced in the more malignant forms and in isolated cases diagnosed as low-grade astrocytomas. Again, no oligodendroglial tumor displayed losses of chromosome 10. In contrast, four tumors with major oligodendroglial component showed losses involving 9p markers, primarily interferon A and B (IFNA, IFNB); this feature was also observed in two low-grade astrocytomas and in 11 high-grade tumors. Isolated cases displayed LOH for markers on chromosomes 13 and 22, whereas EGFR amplification was almost exclusively evidenced in the more malignant forms which, in most instances, also presented LOH for chromosome 10. In general, the samples with lower malignancy stage displayed a lesser grade of abnormalities, mainly restricted to losses at 17p and chromosome 10 in astrocytomas grade I-II and at 9p in oligodendrogliomas. In contrast, about 50% of the high-grade tumor samples analyzed included abnormalities at two or more loci, with a recurrent association of EGFR amplification and LOH for chromosome 10; this association was evident in 26% of the high-grade astrocytomas.

Adult↗
PubMed1993

Clonal chromosome aberrations in neurinomas.

Chromosome studies were performed after short-term in vitro culture of 39 samples from neurinomas and two samples from malignant schwannomas. Clonal abnormalities involving chromosome 22 were observed in 23 cases, as the sole chromosomal deviation in 12 of them. In 11 samples, other clonal numerical and/or structural aberrations were detected in addition to loss of chromosome 22, either in the same cells or in cells other than those having monosomy 22. Within the group of neurinomas with no involvement of chromosome 22, there were again two cytogenetically distinctive subgroups: one with an abnormal karyotype, and the second with a normal chromosome complement. Our findings confirm that monosomy 22 is a characteristic feature of this type of neoplasm, but also suggest the existence of different cytogenetic subgroups of neurinomas.

Chromosome Aberrations↗
PubMed1993

Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches.

Southern blot hybridization studies were performed on a panel of 130 blood/tumor samples from brain neoplasms including all major histologic subtypes: 50 meningiomas, 18 neurinomas, 56 gliomas, and six others. To detect abnormalities involving chromosome 22, polymorphic probes were used to analyze eight loci located in this chromosome: D22S9, IGLV, D22S20, D22S32, MB, PDGF-B, D22S80, and D22S171. Loss of heterozygosity (LOH) was observed in 40 cases including monosomy, terminal, and interstitial deletions, which suggest the location of recessive tumor genes in certain chromosome 22 subregions (22q11.3-q12 in neurinomas and meningiomas, and 22q13 in malignant gliomas). Cytogenetic studies were performed in parallel on the same tumors, in most instances corroborating the presence of abnormalities for chromosome 22. Nevertheless, discrepancies between the cytogenetic and molecular findings were observed in several cases, suggesting that the use of both methodologies in combination might provide key information on the incidence and extent of the abnormalities involving chromosome 22 in human brain tumors.

Blotting, Southern↗
PubMed1993

Involvement of 22q12 in a neurofibrosarcoma in neurofibromatosis type 1.

We describe the cytogenetic and molecular genetic findings in a neurofibrosarcoma arising in a patient affected by neurofibromatosis type 1. Multiple chromosomal rearrangements were found but only a few of them were identified as clonal abnormalities, including a deletion of chromosome 22, which at the molecular level proved to be interstitial, mainly involving the 22q12 region. Loss of heterozygosity for markers D22S32 and MB was observed. These findings are in agreement with previous data which suggest a possible involvement of a gene located at 22q11-q13.1 during the neoplastic development of some neurofibromatosis type 1-associated tumors.

Adult↗
PubMed1993

Chromosome 22 heterozygosity is retained in most hyperdiploid and pseudodiploid meningiomas.

Hyperdiploid or pseudodiploid modal chromosome numbers were found characterizing six human meningiomas, and all six tumors were disomic for chromosome 22. The scarce previous reports on the subject suggest that, in these cytogenetic subgroups of meningiomas, duplication of the retained chromosome 22 occurs after the loss of the other member of the pair, thus correlating well with the main characteristic of meningiomas, that is, losses of 22. To verify this question, molecular genetic analyses were performed on DNA pairs from blood and tumoral samples of all six cases, using polymorphic markers for chromosome 22. Restriction fragment length polymorphism studies failed to show any loss of heterozygosity for markers located on this chromosome in all six cases, suggesting that a different mechanism to that previously proposed might take place in the hyperdiploid or pseudodiploid meningiomas; perhaps a submicroscopic involvement (microdeletions or inactivating mutations) of the meningioma locus (both alleles) may result in an effect similar to that produced by monosomy 22 (which probably unmasks recessive mutations on the retained allele), enhancing the development of meningiomas.

Alleles↗
PubMed1992

Loss of heterozygosity for distal markers on 22q in human gliomas.

Loss of constitutional heterozygosity as determined through the analysis of restriction-fragment-length polymorphism (RFLP) on tumoral and constitutional DNA has proven to be helpful to delimit the location of tumor-suppressor genes in the human genome. In malignant gliomas this approach indicates that chromosomes 9p, 10, 17p, and 22 may contain genes of this category involved in its origin and/or progression. Regarding chromosome 22, the data so far provided by molecular studies confirmed those previously reported by cytogenetic studies, suggesting the existence of a sub-group of malignant gliomas characterized by monosomy of this chromosome. However, the precise location of the putative glioma suppressor gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic and RFLP study on a series of 31 gliomas, looking for structural abnormalities of this chromosome. In 3 instances, terminal deletions of the long arm of chromosome 22 were observed by both methodologies, suggesting that the band q13 region distal to the D22S80 marker might be the critical domain non-randomly involved in tumor suppression of gliomas.

Astrocytoma↗