Biomedical subjects

R B Jenkins

Publications and source records attributed to R B Jenkins.

At least 109 records · Page 6Linked to original sources

PubMed1994

Cytogenetic studies of four hemangiopericytomas.

We report cytogenetic studies on four hemangiopericytomas using in situ culture and robotic harvesting. Simple clonal chromosome abnormalities were observed in each of the three successful tumors. A cerebral tumor had a nonconstitutional 46,XX,t(7;12)(p15;q15) karyotype. A recurrent cerebral tumor had two cell lines: one with a 46,XY,t(2;12)(p13;q24.1) karyotype and one with a 46,XY,t(5;7)(q13;p15) karyotype. Each of the metaphases from a lung tumor had a 46,Y,inv(X)(p22.3q13) karyotype. We conclude that simple nonconstitutional balanced chromosome anomalies of 7p15 and 12q are common in cerebral hemangiopericytomas. It is possible that balanced anomalies of these chromosome regions are related to the pathogenesis of this tumor type.

Adult↗

PubMed1994

Chromosomal aneusomies detected by fluorescent in situ hybridization analysis in clinically localized prostate carcinoma.

Fluorescent in situ hybridization using 12 chromosome enumeration probes (for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X and Y) was used to evaluate fresh tumor touch preparations from 40 randomly selected radical prostatectomy specimens. Of the tumors 16 (40%) contained chromosomal aneusomies. Chromosome 8 was aneusomic in 9 tumors (23%). Gain of chromosome 7 was observed in 8 tumors (20%). Chromosome 17 was aneusomic in 4 cases, and chromosomes 10, 11, 12, 18 and Y were each aneusomic twice. Loss of chromosome 9 was observed in 1 tumor. Chromosomes 4, 6, and X were never aneusomic. The percentage of monosomy 17 nuclei was 2 to 4 times the amount noted with the other autosomes for tumor and benign tissue. Computer analysis demonstrated that these signals contained twice the signal density and were significantly different (p < 0.0001) than the single diploid chromosome 17 signals. This result is consistent with homologous pairing of chromosome 17 in benign and neoplastic prostate tissue. Anomalies of chromosomes 8 and/or 7 were present in 14 of the 16 cases (88%) aneusomic by fluorescent in situ hybridization. High grade tumors were more likely to be aneuploid on fluorescent in situ hybridization (p < 0.001). Tumors with chromosome 8 aneusomies were of higher stage (p < 0.05). Fluorescent in situ hybridization is more sensitive than flow cytometry for the detection of aneusomy/aneuploidy. The prognostic relevance of these findings will require further investigation.

Aneuploidy↗

PubMed1994

Aggressive medulloblastoma with high-level N-myc amplification.

A 27-year-old man was treated for an aggressive cerebellar medulloblastoma that, at operation, exhibited dural invasion. Six months after gross total resection and radiation therapy, a "surgical metastasis" developed in the lower portion of the surgical scar. The tumor grew rapidly down into the right side of his neck. Chemotherapy failed, and he subsequently died. Cytogenetic and molecular genetic studies revealed multiple numeric and structural chromosome abnormalities, including an abnormal chromosome 17p arm, more than 100-fold N-myc amplification, a rearranged c-myc gene, and a 16-base pair deletion involving exon 7 of the p53 gene. We postulate that these genetic features may have contributed to the aggressive behavior of the tumor.

Adult↗

PubMed1994

Fluorescence in situ hybridization analysis of trisomy 12 in ovarian tumors.

Conventional cytogenetic studies have suggested that trisomy 12 may be a characteristic nonrandom numerical chromosome anomaly in benign ovarian tumors, particularly sex cord-stromal tumors. To confirm this finding, and to avoid possible culture artifact introduced during cytogenetic analysis, the authors performed fluorescence in situ hybridization (FISH) in paraffin-embedded samples of select ovarian neoplasms. Forty-four ovarian fibromas and granulosa cell tumors and 31 benign and borderline epithelial ovarian tumors were examined for the presence of trisomy 12. Trisomy 12 was detected in 40% (8 of 20) of the fibromas. No evidence of trisomy 12 was present in 24 granulosa cell tumors, although 1 granulosa cell tumor was tetrasomic for chromosome 12. Trisomy 12 was found in 27% (3 of 11) of the serous borderline tumors, but was not observed in any of the benign epithelial tumors (13 serous and 7 mucinous cystadenomas). These results confirm that trisomy 12 occurs in a significant proportion of fibromas. However, the incidence of trisomy 12 in granulosa cell tumors is far lower than suggested by previous studies. These results, in conjunction with those of previous cytogenetic reports, suggest that trisomy 12 is rare in benign epithelial ovarian tumors, but occurs fairly commonly as a sole anomaly in borderline epithelial tumors. Further investigation is necessary to establish the significance of trisomy 12 in the pathogenesis of these tumors.

Chromosomes, Human, Pair 12↗

PubMed1994

Correlation of cytogenetic and fluorescence in situ hybridization (FISH) studies in normal and gliotic brain.

In vitro tissue culturing, for karyotype analysis, may introduce artifacts confounding the cytogenetic evaluation of tissues with low baseline proliferative activity. Utilizing a panel of fluorescence in situ hybridization (FISH) probes for chromosomes 7, 8, 9, 10, 12, 17, 18, X, and Y, we compared the results of FISH analysis of non-tumorous normal (11 patients) and gliotic (10 patients) brain tissue touch preparations with those of cytogenetic evaluation performed on short-term primary cultures of the same material. We found a significant rate of apparent monosomy of chromosomes 8 and 17 by FISH analysis, with no corresponding clonal chromosomal loss detected by karyotype evaluation. These monosomy rates were significantly lower in gliotic than in normal brain tissue, and image analysis suggested that this apparent monosomy was due to interphase pairing of homologous centromere signals. Two distinct Y-chromosome signals were seen in 9.4% of nuclei by FISH, with 3 of 15 males displaying disomy Y rates over 15%. Disomy Y rates correlated approximately with age and clonal disomy Y was seen in the karyotype of one of these specimens. Karyotype analysis demonstrated loss of a sex chromosome in 6 specimens, while no sex chromosome nullisomy was detected by FISH. FISH is a valuable adjunct to the cytogenetic evaluation of tissues with low baseline proliferative activity. The differences in relative monosomy rates between normal and gliotic brain suggest that alterations in nuclear architecture and/or DNA sequence accompany the transition from normal to reactive glia.

Aged↗

PubMed1994

Molecular genetics of astrocytomas and meningiomas.

Although both spatial and temporal heterogeneity confound the description of the genetic events underlying glioma tumorigenesis, it is becoming evident that chromosome 17 loss and p53 inactivating mutations are probably involved early in the pathway of tumorigenesis of some, but not all, astrocytomas. Chromosome 10 loss and epidermal growth factor receptor amplification are seen predominantly in high-grade lesions, although they have not been shown to be independent prognostic indicators. Data is accumulating on the presence of a tumor suppressor gene on chromosome 9p, although the gene remains to be identified. The roles of chromosome 22 and the NF-2 tumor suppressor gene in the tumorigenesis of sporadic and familial meningiomas are discussed here, along with other nonrandom chromosomal alterations that are seen in both astrocytomas and meningiomas.

Adult↗

PubMed1994

Detection of trisomy 12 by FISH in untreated B-chronic lymphocytic leukemia: correlation with stage and CD20 antigen expression intensity.

We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12 for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1). There was a trend toward an higher incidence of trisomy 12 in patients with Rai stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12 had strong intensity CD20 antigen expression compared to 21% (14/68) of patients without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected by FISH with an overall incidence of 20%. This technique should be applied to larger groups of patients to confirm the potential variation among Rai stages and immunophenotypic subgroups.

Antigens, CD↗

PubMed1994

Cytogenetics of prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

This report summarizes the current knowledge with respect to genetic changes associated with the development of prostate cancer. The relation between the occurrence of these changes and the stage of the disease is by far not clear yet, albeit that some tendencies become more or less evident. In Fig. 2 these are summarized. Whereas changes on 7q and loss or gain of the X chromosome are not consistently found by either RFLP or ISH analysis, other changes are (8p-, 10p-, 10q, 16q-, and 18q-). Clearly the picture is far from complete and even more the relevant genes on these chromosomes are not defined. E-cadherin was considered a good candidate and indeed the value as progression marker is great. However, the studies so far indicate that E-cadherin does not behave as a classical type I suppressor gene and the relation with 16q loss remains to be established. The data available to date regarding chromosomal changes in prostate cancer are limited. Many studies have to be pursued to identify the consistent changes, and moreover, to map the relevant loci harbouring the genes that are implicated in the development of this disease. This knowledge will be critical in the design of appropriate diagnostic methods and possibly clues towards therapy.

Cadherins↗

PubMed1993

Comparison of loss of heterozygosity patterns in invasive low-grade and high-grade epithelial ovarian carcinomas.

Loss of heterozygosity (LOH) studies were performed to investigate the genetic differences which separate low-grade (LG), high-grade (HG), and borderline epithelial ovarian carcinomas. Fresh tumor samples and blood were obtained from 58 patients (20 LG, 34 HG, and 4 borderline tumor specimens) undergoing surgery for ovarian carcinoma at Mayo Clinic. Tumors were graded using a modified Broder's classification with invasive grades 1 and 2 considered LG, invasive grades 3 and 4 considered HG, and tumors with no evidence of stromal invasion classified as borderline. Polymorphism analysis was performed using 76 restriction fragment length polymorphisms and variable number of tandem repeats and 59 microsatellite markers representing all chromosome arms. Chromosome arms 6p, 17p, 17q, and 22q were found to be frequently lost in LG as well as HG tumors. Chromosome arms 13q and 15q were lost to a significantly greater extent in HG tumors compared to LG neoplasms (P = 0.003 and P = 0.08, respectively). Conversely, 3p loss was seen more frequently with LG tumors (P = 0.02). The majority of LG tumors (65%) did not show frequent LOH in the allelotype analysis. In fact, a subset of 7 (7 of 20) LG tumors accounted for 76% of the total allelic loss in the LG category. These tumors showed LOH almost identical to that of the HG neoplasms. Borderline tumors showed a low rate of allelic loss. There were no common events found between borderline and invasive tumors. Our data suggest that most HG tumors and a subset of LG tumors share genetic alterations at putative tumor suppressor genes detected by LOH studies. Chromosome 6 and 17 losses appear to be early events while 13q and 15q losses appear to be critical late events. However, a majority of LG tumors appear to develop as a consequence of an alternative mechanism(s) which is not detected by LOH studies. Possibilities include: (a) inactivation of tumor suppressor genes without LOH; (b) dominant negative gene(s) in which only one allele requires mutation; and (c) changes in dominant acting oncogenes. This unidentified phenomenon may be operative in borderline tumors as well.

Alleles↗

PubMed1993

Human epithelial ovarian cancer allelotype.

To determine which chromosomes and chromosomal regions contain putative tumor suppressor genes important for human epithelial ovarian cancer, we performed loss of heterozygosity (LOH) studies on 37 primary epithelial ovarian tumors. Using 70 polymorphic markers, we examined all chromosome arms (excluding acrocentric arms) on all specimens. Our findings show a high frequency of LOH for the following chromosome arms: 5q (43%); 6p (62%); 6q (57%); 7p (36%); 8p (40%); 9q (54%); 13q (56%); 14q (47%); 15q (36%); 17p (81%); 17q (76%); 18q (43%); 21q (36%); and 22q (71%). When separated into low and high grade tumors, there were statistically significant differences of LOH for the following chromosome arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90%); and 17q (29% versus 87%). No statistically significant difference was found between different histological subtypes. The average fractional allelic loss for low grade tumors was 0.17 versus 0.40 for high grade and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 13 (5 markers); chromosome 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor showed deletion of only a portion of chromosome 13. When any informative marker for chromosome 13 showed loss, all markers showed loss. Similarly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p markers was observed in 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at least 2 regions of chromosome 6 are important for ovarian epithelial carcinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus.

Alleles↗

PubMed1993

Absence of prohibitin gene mutations in human epithelial ovarian tumors.

Multiple loss of heterozygosity (LOH) studies of ovarian cancers have found a high incidence of chromosome 17 loss in these tumors. Several authors have suggested that the region commonly deleted encompasses 17q12-21. In addition, this region has recently been reported to be linked to the familial breast/ovarian cancer syndrome. Recently the human prohibitin gene was mapped to region 17q12-22. Prohibitin causes arrest of DNA synthesis by fibroblast and HeLa cells and prohibitin shows significant homology to a gene (Cc) thought to be important for the regulation of development of Drosophila melanogaster. These findings have led many to consider the prohibitin gene a potential tumor suppressor gene. In addition, sequence analysis of exon 4 of human prohibitin gene revealed mutations in 4 of 23 sporadic breast carcinomas. Because of the proposed function for prohibitin, its alterations in breast cancers, and the fact that its location on 17q falls within a commonly deleted region in ovarian cancers, we have undertaken an analysis of the sequence of prohibitin in epithelial ovarian cancers. Using several polymorphic DNA probes, we identified 20 epithelial ovarian tumors which demonstrated LOH for the region that contains the prohibitin gene. To evaluate whether mutations of prohibitin may be important in ovarian carcinogenesis, we have sequenced exons 4 and 5 of this gene using the technique of genomic amplification with transcript sequencing. Only normal exon 4 and 5 sequence was observed among the 20 tumors screened. These results demonstrate that this region of the prohibitin gene is not mutated in epithelial ovarian cancers and suggest that the prohibitin gene does not play a role in ovarian carcinogenesis. Sequencing of further exons and introns are needed to confirm this latter hypothesis.

Base Sequence↗

PubMed1993

Gliosis specimens contain clonal cytogenetic abnormalities.

The relevance of sex chromosome aneusomy and trisomy 7 in neoplastic brain tissue is controversial. For better understanding of the relative importance of these anomalies, we made a conventional cytogenetic study of cells from tissue obtained from patients who underwent partial cerebral resection for a seizure disorder. Each specimen exhibited "gliosis," but none contained histologically identifiable tumor cells. Sixty-six specimens were analyzed by routine cytogenetic methods. Nonclonal abnormalities were observed in 11.6% of the cells (86% of cases) analyzed. In 11 cases, however, simple clonal karyotypes were observed. Of these cases, six involved loss of a Y chromosome and three involved loss of an X chromosome. Among the cases with loss of an X chromosome, two exhibited multiple abnormal clones. One of these cases had trisomy 7 as well as trisomy 18, and another had a supernumerary psu dic(15)(q13). The supernumerary chromosome was constitutional. One patient had possible Klinefelter syndrome. An additional case had a clonal del(10)(q23) that may have resulted from a hereditary fragile site. We conclude that although some of the apparently acquired clonal and nonclonal abnormalities may be due to a consistent in vitro artifact, it is probable that they are present in the brain tissue itself. Whatever the cause, caution should be used in interpretating cytogenetic abnormalities observed in brain tumor specimens.

Adolescent↗

PubMed1993

Cytogenetic studies of epithelial ovarian carcinoma.

We performed cytogenetic studies of 36 human epithelial ovarian carcinomas using in situ culture and robotic harvest. We obtained analyzable metaphases of all 36 tumors (100%). One or more chromosomally abnormal clones were observed in 80% of tumors. Common clonal chromosome gains (each occurring in six or more cases) included +1, +2, +3, +6, +7, +9, and +12. Common clonal chromosome losses (occurring in 12 or more cases) included -X, -4, -8, -11, -13, -15, -17, and -22. Common clonal structural abnormalities (occurring in four or more cases) involved regions 1p36, 1q32, 1q42, 3p13-->p26, 3q26-->q29, 7p22, 9q34, 11p13-p15, 17q21-->q23, 19p13.3, and 19q13.3. Trisomy 12 was noted as the sole anomaly in three of five borderline and grade 1 tumors. Two grade 2 tumors contained i(1q), -14, -15 and -22. The results suggest that the pathogenesis of borderline and low-grade tumors may differ from that of higher grade tumors. Two high-grade tumors had an apparent translocation between 17q21 and 19p13.3, two chromosome regions believed to be critical to ovarian carcinogenesis.

Adenocarcinoma↗

PubMed1993

Karyotypic analysis in primary myelodysplastic syndromes.

Cytogenetics has provided new insights into the biology and pathogenesis of myelodysplastic syndromes. In patients with refractory anemia, it has provided proof of clonality and has helped differentiate chronic myelomonocytic leukemia from chronic myeloid leukemia. As a prognostic tool, cytogenetics has been predictive of duration of survival and leukemic transformation. However, its role as an independent prognostic factor compared with recent prognostic scoring systems remains to be determined. New techniques such as fluorescent in situ hybridization using chromosome-specific DNA probes may expand the usefulness of cytogenetics. The prognostic impact of cytogenetics may not be fully realized until more effective treatments become available.

Adult↗

PubMed1993

Use of fluorescent in situ hybridization for deoxyribonucleic acid ploidy analysis of prostatic adenocarcinoma.

Fluorescent in situ hybridization using 2 chromosome specific centromere probes was evaluated as a method of ploidy analysis in touch preparations from 50 radical prostatectomy specimens. Tumors were classified as aneuploid by fluorescent in situ hybridization when nuclei had an abnormal copy number (aneusomic) for either chromosome centromere 8 or 12. Tetraploid tumors were defined as those with 4 copies (tetrasomic) of chromosome centromeres 8 and 12. The fluorescent in situ hybridization ploidy patterns were compared to the deoxyribonucleic acid (DNA) ploidy patterns subsequently obtained by flow cytometry on the same tissue following paraffin embedding. Concordant fluorescent in situ hybridization and flow cytometry ploidy classification was obtained in 82% of the cases (p < or = 0.0001). Of 7 aneuploid tumors 3 were identified by both methods. Trisomy 8 was detected by fluorescent in situ hybridization in 3 cases that were classified as DNA diploid (2 tumors) and DNA tetraploid (1 tumor). Conversely, flow cytometry detected aneuploidy (hypotetraploidy) in 1 tumor when the fluorescent in situ hybridization results were consistent with tetraploidy. Overall, fluorescent in situ hybridization was more sensitive in aneuploidy detection (6 of 7 cases) than flow cytometry (4 of 7). Of 19 tetraploid cases 5 had discordant fluorescent in situ hybridization and flow cytometry results. However, all 5 cases contained low levels of tetraploidy and the discrepant results were most likely due to the limits of precision of 1 or both methods. In conclusion, we demonstrated that fluorescent in situ hybridization ploidy analysis can be rapidly performed on fresh touch preparations of prostate tissue. This preliminary study demonstrates that the ploidy result determined by fluorescent in situ hybridization correlates well with that obtained by flow cytometry. More complete fluorescent in situ hybridization studies of prostate carcinoma will require additional probes for other chromosomes.

Adenocarcinoma↗

PubMed1993

Interphase molecular cytogenetic analysis of epithelial ovarian carcinomas.

Karyotype information on ovarian carcinomas has been limited because the tumors are often difficult to culture and the resultant metaphases can have complex numerical and structural chromosomal anomalies. Fluorescent in situ hybridization is a rapid method of determining centromere copy number in metaphase cells and interphase nuclei. Fluorescent in situ hybridization was used to determine the numerical centromere complement of chromosomes X, 8, 12, and 17 and HER-2/neu gene amplification within interphase nuclei of 25 primary epithelial ovarian carcinomas. Touch preparations of the carcinomas were hybridized with two-color combinations of directly labeled alpha-satellite centromeric chromosome enumeration probes and a directly labeled HER-2/neu probe. Modal centromere copy numbers for each of the four chromosomes were used to determine numerical abnormalities relative to the flow cytometric DNA ploidy level for each tumor. Four cases were found to be normal with respect to the four chromosomes studied. In the remaining 21 cases a relative loss of chromosomes 17 (16 cases) and X (nine cases) and a relative gain of chromosomes 12 (10 cases) and 8 (nine cases) were the most common findings. In addition, the HER-2/neu gene was amplified in two of the 25 tumors. In conclusion, fluorescent in situ hybridization is an excellent method for rapid determination of numerical abnormalities and gene amplification in ovarian carcinomas.

Biomarkers, Tumor↗

PubMed1993

Fluorescence in situ hybridization with X and Y chromosome probes for cytogenetic studies on bone marrow cells after opposite sex transplantation.

We investigated the efficacy of fluorescence-labelled chromosome probes (CEP-X/Y) for the X and Y chromosomes to study patients who have had opposite sex BMT. These probes hybridize to the centromere region of the X chromosome and nearly the entire long arm of the Y chromosome. These probes are direct-labelled and produce X and Y signals that can be simultaneously viewed and readily distinguished from each other by color and size after only five brief washes. We investigated BM specimens from 20 normal donors and 16 patients who had undergone an opposite sex BMT. We found no significant interinvestigator differences with respect to scoring XX or XY interphase cells. The 'normal range' for XX cells in males was up to 0.628% and for XY cells in females it was up to 0.299%. Each of the specimens from the patients who underwent BMT had a significant number of donor cells compared with normal range. We suggest that an economical, rapid and accurate cytogenetic test can be achieved by using these probes as an adjunct to conventional cytogenetics.

Bone Marrow↗

PubMed1992

Cytogenetic analysis of six renal oncocytomas and a chromophobe cell renal carcinoma. Evidence that -Y, -1 may be a characteristic anomaly in renal oncocytomas.

Renal oncocytomas are benign tumors whose morphologic features may sometimes be confused with those of certain low-grade malignant neoplasms of the kidney, e.g., chromophobe cell and granular cell variants of renal carcinoma. The presence of a specific genetic abnormality might help differentiate these tumors. Because very few cytogenetic studies of renal oncocytomas have been published, we investigated a consecutive series of six such tumors. We also performed chromosome analysis on a chromophobe cell carcinoma because cytogenetic analyses of this tumor have not been previously reported. Tumor cell metaphases were analyzed after mechanical and enzyme disaggregation, in situ culture, and robotic harvesting. Clonal abnormalities were present in five of the six oncocytomas, and loss of chromosome 1 with loss of the Y chromosome occurred in two. Review of the literature disclosed four other renal oncocytomas with the 44,X,-Y,-1 karyotype. In the chromophobe cell carcinoma, we noted an abnormal clone with a del(11)(p12p15.1); similar anomalies were not observed in the renal oncocytomas. We conclude that renal oncocytomas have clonal chromosome abnormalities and that a subgroup of these tumors may be specifically associated with loss of chromosomes 1 and Y. Because this is a small series, further investigation may help establish whether cytogenetic studies can provide diagnostic and pathogenic information about renal oncocytomas.

Adenoma↗