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P Radice

Publications and source records attributed to P Radice.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analysis of the neurofibromatosis type 2 gene in different human tumors of neuroectodermal origin.

The autosomal dominant syndrome neurofibromatosis type 2 (NF2) is characterized by the development of bilateral vestibular schwannomas, meningiomas, ependymomas and gliomas. The NF2 gene, recently isolated from chromosome 22, is mutated in both sporadic and NF2 tumors such as schwannomas, meningiomas and ependymomas. Mutations of the gene have been described not only in the neoplasms usually associated with NF2, but also in 30% of the melanomas and 41 % of the mesotheliomas analyzed. In particular, the finding of mutations in melanomas supports the hypothesis that the NF2 gene is involved in the genesis of several tumor types that arise from the embryonic neural crest. In this study we examined, by single-strand conformational polymorphism (SSCP) analysis, 41 tumors of the central nervous system (11 schwannomas and 30 gliomas), 19 melanomas and 15 Merkel cell carcinoma specimens for mutations in the coding sequence of the NF2 gene. We found three inactivating mutations of the NF2 gene in schwannomas. No alterations of the gene were detected by SSCP analysis of the other tumors. These results confirm the role of NF2 in pathogenesis of schwannomas, but do not define its significance in the genesis of the other neuroectodermal tumors studied.

Central Nervous System Neoplasms↗
PubMed1995

Allelotyping in Wilms tumors identifies a putative third tumor suppressor gene on chromosome 11.

An analysis of loss of heterozygosity for markers on both the short and the long arm of chromosome 11 was performed in 24 sporadic Wilms tumors. Six cases (25%) showed allelic losses involving the entire chromosome. In one case (4%) the loss was restricted solely to the WT1 gene on band p13. Two cases (8%) displayed allelic losses for WT1 and for markers on band p15.5, where the putative tumor suppressor gene WT2 has been mapped, but retained heterozygosity for markers on the long arm. In three tumors (13%) the loss of heterozygosity involved markers mapped to chromosomal regions p15.5 and q23.3-qter, but did not affect WT1 and markers on q12-q13. Altogether, the proportion of cases showing allelic losses at the distal region of 11q (37%) was comparable to that of cases with LOH affecting the WT1 (37%) or the WT2 (46%) loci, thus suggesting the existence of a third chromosome 11 tumor suppressor gene involved in the pathogenesis of Wilms tumors.

Alleles↗
PubMed1995

The human archain gene, ARCN1, has highly conserved homologs in rice and Drosophila.

A novel human gene, ARCN1, has been identified in chromosome band 11q23.3. It maps approximately 50 kb telomeric to MLL, a gene that is disrupted in a number of leukemia-associated translocation chromosomes. cDNA clones representing ARCN1 hybridize to 4-kb mRNA species present in all tissues tested. Sequencing of cDNAs suggests that at least two forms of mRNA with alternative 5' ends are present within the cell. The mRNA with the longest open reading frame gives rise to a protein of 57 kDa. Although the sequence reported is novel, remarkable similarity is observed with two predicted protein sequences from partial DNA sequences generated by rice (Oryza sativa) and fruit fly (Drosophila melanogaster) genome projects. The degree of sequence conservation is comparable to that observed for highly conserved structural proteins, such as heat shock protein HSP70, and is greater than that of gamma-tubulin and heat shock protein HSP60. A more distant relationship to the group of clathrin-associated proteins suggests a possible role in vesicle structure or trafficking. In view of its ancient pedigree and a potential involvement in cellular architecture, we propose that the ARCN1 protein be named archain.

Amino Acid Sequence↗
PubMed1995

Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions.

Patients with a primary cancer in the lung or in the upper aerodigestive tract have an increased risk of developing synchronous or metachronous second primary lung tumors. This phenomenon has been related to the chronic exposure of the bronchial tree to carcinogens through a so-called "field cancerization" process. This study was designed to investigate at the somatic level the genetic basis of the field cancerization effect in patients having multiple simultaneous neoplastic and preneoplastic lesions of the lung. The pattern of specific genetic changes occurring with high frequency and in early stages of lung carcinogenesis including p53 mutations, deletions of chromosome 3p, and K-ras mutations, was investigated by immunocytochemical, cytogenetic, and molecular approaches in 11 synchronous lesions of five patients with multiple lung cancers. Different genetic lesions were observed in all of the pathological specimens analyzed from each patient. The pattern of these changes was different both in topographically distant or adjacent lesions and in tumors with the same histopathological diagnosis supporting their independent origin. The present data provide further evidence of the clinical relevance of the field cancerization process, and support the use of genetic markers in the differential diagnosis of recurrence or metastasis versus second primaries of the lung.

Adenocarcinoma↗
PubMed1995

Modulation of markers associated with tumor aggressiveness in human breast cancer cell lines by N-(4-hydroxyphenyl) retinamide.

The retinoid N-(hydroxyphenyl) retinamide (4-HPR) appears to be a promising tool for chemoprevention of breast carcinoma, and clinical trials to evaluate its effect are in progress. However, its action on tumor cells has remained largely undefined. We report here that 4-HPR induced apoptosis and/or differentiation in breast cancer cell lines, independent of hormone receptor status and retinoic acid receptor expression, although it was slightly more efficient in inhibiting proliferation of estrogen receptor-positive cells. 4-HPR up-modulated expression of several differentiation markers (class 1 HLA, laminin, and beta 1 integrin chain) and down-regulated expression of molecules associated with tumor progression, including the p185/HER2 oncoprotein, the epidermal growth factor receptor, and the M(r) 67,000 laminin receptor. These data suggest that 4-HPR could exert a beneficial effect by inhibiting cell proliferation and modulating breast tumor aggressiveness.

Anticarcinogenic Agents↗
PubMed1993

A panel of sequence tagged sites for chromosome band 11q23.

A panel of sequence tagged sites (STSs) representing 30 markers previously assigned to human chromosome band 11q23 has been assembled. Eleven STSs represent cloned genes, and the remainder are from anonymous DNA segments. The STSs have been used in PCR experiments to localize their cognate sequences further with respect to five translocation breakpoints that define three intervals in 11q23. Two of these translocation breakpoints have been mapped more precisely by the STS assignments. The STS panel will form a useful starting point for the generation of a genomic contig of band 11q23.

Base Sequence↗
PubMed1992

Distinct breakpoints in band 11q23 of the t(4;11) and t(11;14) associated with leukocyte malignancy.

Several non-random translocation breakpoints associated with leukemia or lymphoma have been shown to occur in chromosome band 11q23 between the genes CD3G and PBGD, a distance of approximately 750 kb. A combination of yeast artificial chromosome (YAC) cloning, in situ hybridization, and pulsed field gel electrophoresis (PFGE) experiments has further refined the interval containing one of these breakpoints, t(4;11)(q21;q23), to within 200 kb of CD3G. We have extended the PFGE analysis to show that the t(4;11) breakpoint lies in a region of approximately 100 kb, situated 100 kb distal to CD3G. Furthermore, we show that a second 11q23 breakpoint, t(11;14)(q23;q32), which was also previously mapped between CD3G and PBGD, is distinct from that of the t(4;11) chromosome. The 11q23 sequences that are involved at the t(11;14) breakpoint are not present in a YAC containing the t(4;11) breakpoint. The t(11;14) breakpoint has been localized on the PFGE map of the CD3G-PBGD interval and is at least 110 kb distal to the t(4;11) breakpoint, thus demonstrating heterogeneity among 11q23 breakpoints.

Base Sequence↗
PubMed1991

The human tropomyosin gene involved in the generation of the TRK oncogene maps to chromosome 1q31.

The chromosomal localization of hTMnm, a gene coding for a cytoskeletal tropomyosin non-muscle isoform involved in the activation of the TRK proto-oncogene in various human tumors, was determined by Southern blot analysis of a panel of human-rodent somatic cell hybrids. Using as a probe an Alu-free intronic fragment related to the tropomyosin sequence fused to the TRK tyrosine kinase domain, the hTMnm gene was assigned to the long arm of chromosome 1. Subsequently, in situ hybridization of the same probe to human metaphase chromosomes localized the hTMnm gene to 1q31. Since we have recently assigned the TRK locus to chromosome 1q32-q41, the generation of the hybrid transforming sequence tropomyosin-TRK may be due to an intrachromosomal rearrangement of the long arm of chromosome 1.

Blotting, Southern↗
PubMed1991

Refined localization to contiguous regions on chromosome 10q of the two genes (H4 and RET) that form the oncogenic sequence PTC.

In this report we confirm the localization of the human RET proto-oncogene to chromosome 10q11.2, both by Southern blot analysis of a panel of human-rodent somatic cell hybrids and by in situ hybridization on human metaphase chromosomes. Previously, we had assigned to the same chromosome region the gene termed H4. In about 25% of papillary thyroid carcinomas, this gene was shown to rearrange with RET to give rise to the transforming sequence PTC. The analysis of different cell hybrids containing subfragments of chromosome 10, in conjunction with pulse field gel electrophoresis, established that H4 is mapped distally to RET at a distance not less than 280 kb. These findings suggest that intrachromosomal rearrangements are responsible for PTC activation in papillary thyroid carcinomas.

Carcinoma, Papillary↗
PubMed1990

Human TRK proto-oncogene maps to chromosome 1q32-q41.

The chromosomal localization of TRK, a gene coding for a putative receptor molecule with an associated tyrosine kinase activity that we have found activated in 25% of patients with papillary thyroid carcinoma, was determined by Southern blot analysis of a panel of human-rodent somatic cells using a cDNA clone containing the entire human TRK proto-oncogene (Martin-Zanca et al., 1986). The TRK gene was assigned to chromosome 1. One hybrid that had retained only the short arm of the human chromosome 1 was negative. Subsequently, in situ hybridization of the same probe to human metaphase chromosomes localized the TRK gene to 1q32-q41.

Blotting, Southern↗
PubMed1989

Onco-suppressor genes in human cancer.

The analysis of the molecular mechanisms governing multistep carcinogenesis became experimentally approachable since the identification and characterization in tumor cells of altered or activated versions of cellular genes (oncogenes) that normally control cell growth and differentiation. The activating mutations confer new properties to the oncogene products and should therefore be considered as gain of function mutations. In addition, the oncogenes appear to act as dominant genetic traits since they act also in the presence of the homologous wild-type allele. However, the concept of a dominance of the transformed phenotype has been challenged by early experiments with somatic cell hybrids which showed that the fusion of normal and malignant cells may suppress the tumorigenic phenotype. The suppression or reversion of the malignant phenotype by the introduction of a normal chromosome into a tumor cell line has lent support to the idea that a family of cellular genes are coding for factors capable to interact with the cell-growth control machinery. These genes seem to reconstitute the normal control of cell growth even in the presence of an activated oncogene. In addition, a two-mutation model has been proposed to explain the epidemiological and clinical features of childhood cancers. According to the model, the development of these malignancies can be caused by the loss or inactivation of both alleles of cellular genes, as suggested by the somatic cell hybrid experiments where the function of the inactivated genes is restored by the contribution of those derived from the normal parental cells. This family of genes is designated as onco-suppressor genes since their product is necessary for the normal regulated cell growth and is lacking or inactivated in malignant cells. At gene level they should be considered as recessive genetic traits, since the tumor phenotype appears when both alleles of an onco-suppressor gene are inactivated. The mutations affecting their normal functions belong to the type "loss of function". The molecular analysis of retinoblastoma has led to the cloning and sequencing of the related onco-suppressor gene (RB gene) whose product displays the features of a gene-regulatory protein. In addition, a binding between the RB product and various viral onco-proteins (E1A, large T, E7) has been demonstrated, thus suggesting a mechanism of RB inactivation by which some DNA viruses can transform the host cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1989

Loss of heterozygosity in human germinal tumors.

The frequency of losses of heterozygosity has been investigated in 14 germinal tumors of the testis. Nonrandom deletion of whole or part of chromosome 11 was observed in four cases. In addition, loss of heterozygosity of all the informative loci analyzed was detected in one ovarian teratoma, indicating its post-meiotic origin. These results suggest that different genetic mechanisms (chromosomal deletions or meiotic segregation) that unmask putative recessive mutations are involved in the onset of germinal tumors.

Biomarkers, Tumor↗