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Biomedical subjects

R B Jenkins

Publications and source records attributed to R B Jenkins.

At least 127 records · Page 7Linked to original sources
PubMed1992

Fluorescence in situ hybridization: a sensitive method for trisomy 8 detection in bone marrow specimens.

Trisomy 8 is a common anomaly in bone marrow (BM) cells of patients with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), or acute nonlymphocytic leukemia (ANLL). We studied the efficacy of fluorescence in situ hybridization (FISH) detection of trisomy 8 in patients with MPD, MDS, or ANLL using directly labeled fluorescent alpha-satellite and whole chromosome paint (WCP) DNA probes specific for chromosome 8. Using FISH, we analyzed interphase nuclei and metaphase spreads from randomized series of BM specimens from normal individuals and patients with varying proportions of trisomy 8 as determined by conventional cytogenetic analysis. The BM of all normal donors contained less than or equal to 2.0% nuclei with 3 interphase FISH signals and less than or equal to 1 metaphase with 3 WCP FISH signals. Ninety-five percent and 98% of BM specimens with at least two metaphase cells with trisomy 8 by cytogenetic analysis contained greater than 2.0% nuclei with 3 interphase FISH and greater than 2 metaphases with 3 WCP FISH signals, respectively. Thirteen patients had 1 in 20 or 1 in 30 metaphase cells with trisomy 8 by conventional cytogenetic studies. Of these patients, four had greater than 2.0% nuclei with 3 interphase FISH signals. The BM of all four patients contained positive metaphase FISH results. We then studied the usefulness of FISH analysis to detect occult trisomy 8 by analyzing BM nuclei from 144 patients who had MPD, MDS, or ANLL and either 20 normal metaphase cells or an abnormal karyotype without trisomy 8. Seven patients had greater than 2.0% nuclei with 3 interphase FISH signals (range, 2.10% to 3.40%) and six patients had 2 or more cells with trisomy 8 upon metaphase FISH or extensive conventional cytogenetic analysis. Our results show that interphase and metaphase FISH analyses are useful methods to detect trisomy 8 cells in BM specimens, especially for specimens with normal or uncertain conventional cytogenetic results.

Bone Marrow↗
PubMed1992

Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas.

Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The alpha-, beta-, and omega-interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.

Brain Neoplasms↗
PubMed1992

Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC.

RET/PTC is a transforming sequence created by the fusion of the tyrosine kinase domain of the RET protooncogene with the 5' end of the locus D10S170 designated by probe H4 and is frequently found activated in human papillary thyroid carcinomas. RET and D10S170 have been mapped to contiguous regions of the long arm of chromosome 10: q11.2 and q21, respectively. To identify the mechanism leading to the generation of the oncogenic sequence RET/PTC, a combined cytogenetic and molecular analysis of several cases of papillary thyroid carcinomas was done. In four cases the results indicated that these tumors had RET/PTC activation and a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with breakpoints coincident with the regions where RET and D10S170 are located. Therefore, a chromosome 10q inversion provides the structural basis for the D10S170-RET fusion that forms the hybrid transforming sequence RET/PTC.

Blotting, Southern↗
PubMed1992

Prognostic value of cytogenetic analysis in human cerebral astrocytomas.

Cytogenetic analysis has become an important part of the diagnostic evaluation of most hematological neoplasms. However, there is limited information on the value of cytogenetic analysis in most solid tumors, including cerebral astrocytomas. This report summarizes a prospective cytogenetic study of 99 human cerebral astrocytomas, 16 mixed oligoastrocytomas, and 2 gliosarcomas. The cytogenetic procedure involved in situ culture and robotic harvesting techniques. Correlative clinical and survival data were available on all patients. We successfully cultured and obtained suitable metaphases in 107 of the 117 tumors. One or more chromosomally abnormal clones were observed in 72 tumors, and nonclonal or normal karyotypes were observed in 35 tumors. In a multivariate analysis, survival time was significantly better in patients whose tumors had normal or nonclonal karyotypes on cytogenetic analyses than in those whose tumors had clonal abnormalities (p = 0.0071). Our study demonstrates that cytogenetic analysis provides independent prognostic information in patients with cerebral astrocytomas.

Astrocytoma↗
PubMed1992

Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas.

Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas.

Adolescent↗
PubMed1992

Fluorescent in situ hybridization: use of whole chromosome paint probes to identify unbalanced chromosome translocations.

By identifying structural chromosome anomalies, the clinical cytogenetics laboratory can play a critical role in the diagnosis and treatment of patients with birth defects. Although many new staining techniques have been developed throughout the years to aid in the detection of anomalous chromosomes, some abnormalities still pose a special challenge to cytogeneticists. This difficulty is especially evident in patients with an abnormal chromosome that does not produce a recognizable banding pattern by conventional staining techniques. We describe a recently discovered method of identifying chromosomes by using whole chromosome-specific DNA probes and fluorescent in situ hybridization and provide examples of how this new procedure facilitated the identification of chromosome abnormalities in two patients with multiple birth defects.

Adult↗
PubMed1992

A genetic review of complete and partial hydatidiform moles and nonmolar triploidy.

Complete and partial hydatidiform moles are genetically aberrant conceptuses. Usually, complete moles have 46 chromosomes (diploidy), all of paternal origin. Most partial moles have 69 chromosomes (triploidy), including 23 of maternal origin and 46 of paternal origin. Triploidy that involves 23 paternal chromosomes and 46 maternal chromosomes is not associated with molar placental changes and, rarely, can result in a live-born infant with multiple birth defects. Herein we review the mechanisms of fertilization that may produce these unbalanced sets of parental chromosomes and the role of genomic imprinting as a possible explanation for these clinical conditions.

Female↗
PubMed1992

Refractory thrombocytopenia. A myelodysplastic syndrome that may mimic immune thrombocytopenic purpura.

The French-American-British classification scheme of myelodysplastic syndromes includes a category of refractory cytopenia that includes refractory thrombocytopenia (RTC). Because dysmegakaryopoiesis manifesting as an isolated cytopenia can be difficult to identify morphologically and because it may be accompanied by megakaryocytic hyperplasia, RTC may be confused with idiopathic thrombocytopenic purpura. A review of 1,220 cases of myelodysplastic syndromes at Mayo Clinic Jacksonville and Mayo Clinic Rochester from 1979 to 1990 yielded 9 cases (0.7%) of isolated thrombocytopenia (RTC) associated with clonal chromosome abnormalities. Review of 319 marrow chromosome analyses performed at the cytogenetics laboratory at Mayo Clinic Rochester from 1979 to 1990 for patients with low platelet count yielded two additional cases of RTC (0.6%). Of the 11 RTC cases, 3 previously had been misdiagnosed as idiopathic thrombocytopenic purpura. All patients had oval macrocytes in peripheral blood smears and abnormal megakaryocyte morphology in bone marrow aspirates, lacked antiplatelet antibodies, and did not have splenomegaly on clinical examination. The most common clonal chromosome abnormalities involved chromosomes 3, 5, 8, or 20. Steroid therapy was ineffective. Clinical and laboratory findings can establish the diagnosis of RTC and allow the physician to avoid recommending inappropriate therapy (steroids or splenectomy) for these patients.

Aged↗
PubMed1992

Medulloblastoma: II. A pathobiologic overview.

The pathobiology of medulloblastoma is reviewed in light of emerging data regarding its immunocytochemical and cytobiologic, as well as molecular biologic, characteristics. The nature of the lesion, particularly its nosologic relation to primitive neuroectodermal tumor, is discussed, as is its place in the World Health Organization classification of tumors of the central nervous system.

Cell Transformation, Neoplastic↗
PubMed1991

Telomeric associations and consistent growth factor overexpression detected in giant cell tumor of bone.

Tumor specimens from 15 patients with giant cell tumor (GCT) of bone were cytogenetically analyzed. A subset of five individuals had tumor cells harvested and polyadenylated RNA isolated. Multiple Northern blots were performed utilizing radiolabeled probes for the growth factors TGF beta 1, TGF beta 2, TGF beta 3, and TGF alpha (TGF, transforming growth factor). RNAs from other types of neoplasms and nonneoplastic cells were examined as controls. The most consistent cytogenetic abnormality detected involved multiple telomeric associations (TAs), most frequently involving the terminus of the long arm of chromosome 19 (19q). Northern blot analysis revealed a consistent expression of TGF beta 1 and TGF beta 2 with an inconsistent mRNA expression for the other TGFs. There was a relative overexpression of mRNA for TGF beta 2. The gene location for TGF beta 1 is near the 19q terminus and thus it is speculated that TGF beta may play a role in the neoplastic transformation of GCT.

Adult↗
PubMed1991

Use of fluorescent in situ hybridization for marker chromosome identification in congenital and neoplastic disorders.

Identifying marker chromosomes of unknown origin in the clinical cytogenetics laboratory has been a problem historically, despite advances in specialized staining techniques. Determination of the origin of these marker chromosomes in patients with congenital or malignant neoplastic disorders is essential for more complete diagnosis, counseling, and treatment. The authors describe the use of fluorescent in situ hybridization with chromosome-specific alpha-satellite DNA probes to identify the origin of marker chromosomes in two patients with congenital disorders and three patients with malignant neoplastic disorders. The impact of firm identification of the marker chromosome for the diagnosis of these patients is discussed. The authors also discuss the feasibility of using this technique routinely in the clinical cytogenetics laboratory.

Adult↗
PubMed1991

Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers.

Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC). Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has not been reported in these neoplasms. These studies were undertaken to determine if consistent chromosomal abnormalities are associated with thyroid cancer, to determine likely regions for molecular genetic investigations, and to determine if there is allelic loss in thyroid tumors. Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC. Using DNA probes specific for chromosomes 1, 3, 10, 16, and 17, we carried out restriction fragment length polymorphism analysis on 6 FTC, 3 follicular adenomas (FA), and 12 PTC. LOH of all informative loci on chromosome 3p was observed in all 6 FTC, but not in FA or PTC. No LOH was observed for loci mapped to chromosome 10 in PTC. Our results suggest: cytogenetic abnormalities of chromosome 10q are associated with PTC; cytogenetic and molecular abnormalities of chromosome 3 are associated with FTC; and a tumor suppressor gene may be present on the short arm of chromosome 3 important for the development or progression of FTC.

Adenocarcinoma↗
PubMed1990

Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones. Four of the papillary carcinomas had a simple clonal karyotype, and three had no apparent chromosome abnormality. All four abnormal papillary tumors contained an anomaly of a chromosome 10q arm. In one instance, an inv(10)(q11.2q21.2) was observed in a Grade 2 papillary carcinoma as the sole acquired abnormality. In another case, an inversion or insertion involving 10q21.2 was found in a Grade 1 papillary tumor. The karyotype of a third tumor, a Grade 1 papillary carcinoma, was 46,XX,der(5)t(5;10)(p15.3;q11),der(9)t(9;?)(q11;?). A fourth abnormal papillary carcinoma, a Grade 1 tumor, had a t(6;10)(q21;q26.1) as the sole abnormality. Each of the five follicular or anaplastic carcinomas had a complex clonal karyotype. The three follicular carcinomas contained an abnormality of 3p25-p21, along with several other chromosome abnormalities.

Adenocarcinoma↗
PubMed1990

The gene for the human erythropoietin receptor: analysis of the coding sequence and assignment to chromosome 19p.

The full-length coding sequence of the human erythropoietin receptor has been assembled from cDNA and genomic DNA. The derived 508 amino acid sequence is 82% identical to the murine erythropoietin (Epo) receptor with one single residue gap in alignment. There is no major structural difference between the human and murine receptor molecules. Nucleotide sequence homology is, as expected, very high within the coding domain. Unexpectedly, there are two distinct, short stretches of 3' untranslated sequence homology between human and murine cDNAs. The functional significance of this sequence conservation is unknown. The human Epo receptor gene is localized to human chromosome 19p by in situ hybridization. This chromosome assignment is confirmed by hybridization to a panel of sorted human chromosomes.

Amino Acid Sequence↗
PubMed1990

Hematologic disorders in 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome.

To study the role of trisomy 21 in hematologic malignancies, we investigated the hematologic disorders of 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome (DS). The most common hematologic malignancy among the patients with acquired trisomy 21 involved both granulocytic and monocytic lineages. By comparison, the hematologic disorders among the DS patients were predominantly acute lymphocytic leukemia and acute megakaryocytic leukemia. Although our sample was small, our results suggest that most patients with acquired trisomy 21 have different hematologic disorders than individuals with DS. Perhaps the role of trisomy 21 in the development of hematologic malignancy is different in constitutional trisomy 21 than it is in acquired trisomy 21.

Aged↗
PubMed1990

Structure and chromosome localization of the human eosinophil-derived neurotoxin and eosinophil cationic protein genes: evidence for intronless coding sequences in the ribonuclease gene superfamily.

Human genomic DNAs for the eosinophil granule proteins, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), were isolated from genomic libraries. Alignment of EDN (RNS2) and ECP (RNS3) gene sequences demonstrated remarkable nucleotide similarities in noncoding sequences, introns, and flanking regions, as well as in the previously known coding regions. Detailed examination of the 5'-noncoding regions yielded putative TATA and CAAT boxes, as well as similarities to promoter motifs from unrelated genes. A single intron of 230 bases was found in the 5' untranslated region and we suggest that a single intron in this region and an intronless coding region are features common to many members of the RNase gene superfamily. The RNS2 and RNS3 genes were localized to the q24-q31 region of human chromosome 14. It is likely that these two genes arose as a consequence of a gene duplication event that took place approximately 25-40 million years ago and that a subset of anthropoid primates possess both of these genes or closely related genes.

Animals↗