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W Grote

Publications and source records attributed to W Grote.

At least 19 recordsLinked to original sources
PubMed1996

Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours.

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.

Adolescent↗
PubMed1996

Secondary acute leukaemias with 11q23 rearrangement: clinical, cytogenetic, FISH and FICTION studies.

Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML). FAB M5a, one had pro-B-acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. All with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrangement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.

Acute Disease↗
PubMed1996

Detection of the t(14;18) chromosomal translocation by interphase cytogenetics with yeast-artificial-chromosome probes in follicular lymphoma and nonneoplastic lymphoproliferation.

PURPOSE: The aim of this study was to establish a fluorescence in situ hybridization (FISH) technique for the detection of t(14;18)(q32;q21), characteristic for follicular lymphoma (Kiel classification: centroblastic centrocytic [cb-cc] lymphoma). MATERIALS AND METHODS: After the FISH system had been established, parallel studies of lymph node biopsy specimens from 30 patients with cb-cc lymphoma and from 32 patients with nonneoplastic lymphoproliferation were performed by means of chromosome analysis, polymerase chain reaction (PCR), and FISH analysis. Two differently labeled yeast-artificial-chromosome (YAC) probes that contained the entire bcl-2 gene and the C-region of the immunoglobulin H (IgH) gene, respectively, were used to detect t(14;18) by FISH. RESULTS: The presence of the translocation is indicated by a red (Cy3)/green (fluorescien isothiocyanate [FITC]) double signal, which corresponds to the IgH/bcl-2 fusion gene, whereas in normal cells the signals are separate. Control studies showed that the double signal is visible in less than 1% of normal cells. FISH analysis was able to identify the t(14;18) in all cases of cb-cc lymphoma we studied. All bcl-2 breakpoints can be detected. Combined immunophenotyping and interphase cytogenetics demonstrated that t(14;18) was restricted to CD22+ B lymphocytes and never occurred in CD3+ T lymphocytes. In four of 32 cases of nonneoplastic lymphoproliferation, t(14;18) was also detected. CONCLUSION: FISH turned out to be the most sensitive method to detect t(14;18). Our FISH results confirm PCR data from other groups that found evidence for the presence of t(14;18) in nonneoplastic lymphoproliferation. It needs to be determined whether, in morphologically nonneoplastic processes, t(14;18) is associated with an increased risk for the development of non-Hodgkin's lymphoma.

Adult↗
PubMed1996

Translocation t(2;5) is not a primary event in Hodgkin's disease. Simultaneous immunophenotyping and interphase cytogenetics.

A number of neoplastic disorders are characterized by recurrent chromosome aberrations. One of these is the translocation t(2;5), which is found in a considerable percentage of large-cell anaplastic lymphomas. This translocation results in the fusion of two genes, alk and npm. The recent discovery of alk/npm mRNA in 11 of 13 cases of Hodgkin's disease has caused a controversial discussion concerning the question of whether t(2;5) is also present in Hodgkin and Reed-Sternberg cells. We tackled this problem on the molecular cytogenetic level by combined CD30 immunophenotyping and interphase cytogenetics. Using a pair of DNA probes flanking both sides of the npm gene breakpoint at 5q35 we were able to prove, at least in 12 of 13 cases of Hodgkin's disease, that all CD30-positive Hodgkin and Reed-Sternberg cells lacked the translocation t(2;5). Fifteen to forty-five Hodgkin/Reed-Sternberg cells were analyzed per case (mean, 27). Our findings indicate that this translocation is not a primary event in the development of Hodgkin's disease.

Adult↗
PubMed1995

Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease.

In Hodgkin's disease, cytogenetically aberrant clones have been demonstrated in a minority of cases studied. In the remaining cases, only normal metaphases have been found, but it is questionable whether normal karyotypes actually correspond to the pathognomonic Hodgkin and Reed-Sternberg (HRS) cells. Numerical aberrations could be studied by fluorescence in situ hybridization (FISH). However, in Hodgkin's disease, the percentage of tumor cells is mostly below the detection limit of FISH, which is near 1%. With the technique of simultaneous fluorescence immunophenotyping and interphase cytogenetic analysis (FICTION), this problem can be overcome. By FICTION, hybridization signals can selectively be evaluated within the CD30a+ cell population. We have studied 30 cytogenetically analyzed cases of Hodgkin's disease by means of FICTION. In all cases, we found numerical chromosome aberrations within the majority of CD30+ HRS cells. In cases with complex and hyperdiploid karyotypes, the cytogenetic results agreed with the FICTION data. There was considerable variability in the chromosome numbers, demonstrating that karyotype instability is an in vivo phenomenon of HRS cells. Lymphocytes never displayed numerical chromosome changes. Our results indicate that HRS cells regularly exhibit numerical chromosome aberrations and that the chromosome numbers are always in the hyperploid range.

Adult↗
PubMed1995

Kappa- and lambda-positive cells in centroblastic-centrocytic lymphoma (follicular lymphoma) may share a secondary chromosome aberration: reflections on early lymphoma development.

The technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION) was applied in four cases of centroblastic-centrocytic (working formulation: follicular) lymphoma. Our aim in this study was to establish whether secondary chromosome aberrations known from a prior cytogenetic analysis were detectable in both kappa- and lambda-expressing tumor cells from the same lymphoma patient. One of the cases did indeed contain kappa- and lambda-positive tumor cells with trisomy 8. On the basis of our results, we reflect on the events that take place during early development of centroblastic-centrocytic lymphoma.

Chromosomes, Human, Pair 8↗
PubMed1995

Detection of chromosome aberrations in paraffin sections of seven gonadal yolk sac tumors of childhood.

Yolk sac tumors are the most frequent kind of malignant pediatric germ cell tumor and may have a fundamentally different pathogenesis than adult germ cell tumors. Since few cytogenetic studies have been performed so far, in situ hybridization was applied to interphase cell nuclei of seven gonadal yolk sac tumors of childhood in routine paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumors and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, 17 and/or X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). As in adult germ cell tumors, all pediatric gonadal yolk sac tumors had an increased incidence of numerical chromosome aberrations. All tumors showed an overrepresentation of at least three chromosomes. Gains of chromosome 12, which is highly specific in adult germ cell tumors, were diagnosed in six pediatric gonadal yolk sac tumors. The DNA indices determined in the paraffin-embedded tumor material correlated well with the in situ hybridization findings. A chromosome was either over- or underrepresented, compared with the corresponding DNA indices, in only a few cases. The short arm of chromosome 1 in adult germ cell tumors is often involved in structural aberrations. In pediatric germ cell tumors, the short arm of chromosome 1 is also a nonrandom site of structural aberrations. Moreover, the presence of a deletion at 1p36.3 in four out of five tumors suggests that the loss of gene(s) in this region is an important event in the pathogenesis of gonadal yolk sac tumors of childhood.

Adult↗
PubMed1995

Clarification of dubious karyotypes in Hodgkin's disease by simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION).

Cytogenetic studies on Hodgkin's disease (HD) typically reveal very complex karyotypes with a variety of numerical and structural abnormalities. The confusing thing is that about 10% of cases contain relatively discrete chromosome aberrations, for example a simple trisomy or loss of one single chromosome. Whether these karyotypes really correspond to Hodgkin and Reed-Sternberg (HRS) cells is uncertain. They could, for example, represent early stages in the evolution of the karyotype of the pathognomonic HRS cells. On the other hand, they could be artificial events that occur during the cytogenetic procedure. In our experience, isolated loss of the Y chromosome is the most frequent finding of this type. This aberration is usually considered to be a preparation artifact. However, if one takes into account that in HD up to 50% of male cases with complex karyotypes also lack the Y chromosome, a possible relation to HRS cells must be considered. The technique of simultaneous fluorescence immunophenotyping and interphase cytogenetic analysis (referred to as FICTION) is a powerful tool for studying the nature of cytogenetically abnormal cells. With the FICTION technique we studied four cases of HD in which the chromosome analysis had shown only the loss of the Y chromosome. Our aim was to clarify whether these karyotypes corresponded to the CD30-positive HRS cells. In two cases we found that HRS cells actually lacked the Y chromosome. There was strong evidence, however, that the HRS cells additionally had other chromosome aberrations and thus could not correspond to the cytogenetically determined karyotypes.

Cytogenetics↗
PubMed1994

Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics.

Trisomy 3, trisomy 5, and an X additional chromosome are the most frequent chromosome aberrations in angioimmunoblastic lymphadenopathy with proteinemia (AILD)-type T-cell lymphomas. To evaluate the frequency of +3 and +X clones, fluorescence in situ hybridization studies with centromere-specific probes for chromosome 3 and X were done in 41 patients with peripheral T-cell lymphomas (PTL). With this interphase cytogenetic approach, 32 of 41 patients (78%) showed +3 clones, and 14 patients (34%) +X clones. These frequencies far exceeded those observed with metaphase cytogenetics (+3, 41%; +X, 20%). Summing up the results of metaphase and interphase cytogenetics, aberrant clones were found in 37 of 41 patients with PTL (90%) and 32 of 36 patients with AILD-type T-cell lymphoma (89%). Although AILD-type T-cell lymphoma is considered a neoplastic disease, it is an exception in that it shows a high frequency of cytogenetically unrelated clones and single cells that cannot be derived from a common cell of origin because of their completely different karyotypes. In five patients, double hybridization with centromere-specific probes for chromosomes 3 and X showed that these aberrations occurred in different cells. When the results of metaphase and interphase cytogenetics were combined, 17 of 36 patients with AILD-type T-cell lymphoma (47%) had unrelated clones. This high frequency of oligoclonal proliferations may be caused by increased genetic instability and an immune defect resulting in impaired elimination of aberrant cells.

Blood Protein Disorders↗
PubMed1994

Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas.

Cytogenetic studies on lymph node and skin biopsy specimens and peripheral blood in 104 patients with peripheral T-cell lymphomas (PTL) were compared with histopathologic diagnoses made according to the updated Kiel classification. Low-grade lymphomas presented normal metaphases more frequently than high-grade ones (P < .0001). This difference remained significant if cases with greater than 10% and greater than 50% normal metaphases in unstimulated cultures and in cultures stimulated by different mitogens were compared. On the other hand, high-grade lymphomas more often showed aberrant clones (P < .05), triploid to tetraploid clones (P < .0001), and complex clones with more than four chromosome changes (P < .01). Low-grade PTL showed consistent cytogenetic features. Clones with both inv(14)(q11q32.1) and trisomy 8q, mostly caused by i(8q)(q10), were found in all cases of T-cell chronic lymphocytic leukemia (T-CLL) and T-cell prolymphocytic leukemia (T-PLL). Trisomy 3 was observed only in angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type PTL, T-zone lymphoma, and lymphoepithelioid lymphoma. Moreover, the proportion of normal metaphases in these PTL was higher than in the other low-grade PTL (P < .01). On the contrary, T-CLL, T-PLL, and cutaneous T-cell lymphomas (CTCL) showed complex clones (P < .0001), duplications in 6p (P < .01), deletions in 6q (P < .01), trisomy 8q (P < .00001), inv(14) (P < .00001), and monosomy 13 or changes of 13q14 (P < .001) more frequently than the other low-grade PTL. Trisomy 5 and + X predominated in AILD-type PTL. A cytogenetic feature characteristic of AILD-type PTL and CTCL was unrelated clones, which were found in 15% of AILD-type PTL and 17% of CTCL. The only chromosome aberration restricted to a certain high-grade PTL was t(2;5)(p23;q35) in large-cell anaplastic lymphoma. Deletions in 6q, total or partial trisomies of 7q, and monosomy 13 or changes of 13q14 turned out to be significantly more frequent in high-grade than in low-grade lymphomas (P < .01, P < .01, and P < .05, respectively). In summary, the cytogenetic findings in our series of 104 PTL enabled us to distinguish not only between low-grade and high-grade lymphomas but also between various entities of PTL. Thus, the cytogenetic findings paralleled the histopathologic diagnoses made according to the updated Kiel classification.

Chromosome Aberrations↗
PubMed1994

Operative treatment and prognosis of syringomyelia.

Twenty-two patients suffering from syringomyelia were treated operatively. Different shunt procedures were performed. Most often syringo-subarachnoid shunt (seven cases) and syringopleural shunt (eight cases) were used. Operative findings and complications were discussed. Postoperative improvement was observed in five patients, twelve were stable-unchanged, four showed further deterioration and one died. Operative treatment should be performed before gross neurological deficit is established.

Adolescent↗
PubMed1994

Recurrent chromosome abnormalities in peripheral T-cell lymphomas.

Cytogenetic findings in 45 cases of peripheral T-cell lymphomas (PTL) diagnosed according to the updated Kiel classification are reported. Recurrent numerical chromosome aberrations comprised -X, -Y, -13, +X, +3, +5 and +7. Recurrent structural aberrations included t/del(1)(p31-32), t(2;5)(p23;q35), dup(5)(q23q31-32), t/dup(6q), t/del(6q), trisomy 7q, and trisomy 8q, mostly due to i(8)(q10), and changes in 14q11 and 14q32.1, mostly due to inv(14)(q11q32.1), t/del(13)(q14), t(6;7)(q13;q13), and t(13;17)(q11-13;p11). All deletions in 6q involved band 6q21 and all partial trisomies of 7q led to an amplification of band 7q21. Further studies are needed to ascertain whether these cytogenetic findings in PTL are of clinical and prognostic significance.

Adolescent↗
PubMed1994

Translocation (X;8)(q2?6;q21.3) in a case of systemic mastocytosis.

Mastocytosis is a rare disease which occasionally progresses into mast cell leukemia or other myeloid neoplasms. Here we report on a patient with systemic mastocytosis who was found to have a clone with t(X;8)(q2?6;q21.3) and two copies of der(8)t(X;8). In accordance with these results, interphase cytogenetic analysis revealed that 93% of bone marrow cells contained three centromeric regions of chromosome 8. We suggest that the t(X;8) and the duplication of the translocation chromosome 8 may play a role in the progression of the diseases.

Aged↗
PubMed1994

Combined immunophenotyping and karyotyping in peripheral T cell lymphomas demonstrating different clonal and nonclonal chromosome aberrations in T helper cells.

Combined immunophenotyping and karyotyping was performed in seven cases of peripheral T cell lymphoma with complex aberrant clones. Various lymphocytic cell populations entered mitosis, whereas all aberrant cells belonged to the T helper/inducer cell population. Lymphomas with the same recurrent chromosome aberrations, i.e. inversion inv(14)(q11q32.1) and isochromosome i(8)(q10), had a very similar immunophenotype. The aberrant cells in these cases expressed CD3+, CD4+, CD7+, CD45RO+. The immunophenotypic similarity is underlined in one case of T prolymphocytic leukemia, in whom the aberrant cells lost the CD8 antigen originally present, during cultivation with PHA. In one case of Sézary's syndrome, two or possibly even three different clones as well as nonclonal aberrations were identified within the T (helper/inducer) cell population, providing further evidence that chromosomal instability is a characteristic feature of cutaneous T cell lymphoma.

Adult↗
PubMed1994

Cytogenetic findings and results of combined immunophenotyping and karyotyping in Hodgkin's disease.

Cytogenetic studies were performed in 21 cases of Hodgkin's disease. Fourteen cases revealed chromosomally aberrant clones which could be fully described in 12 cases. Two cases showed different unrelated clones and five cases only single cell aberrations. Recurrent breakpoints were 1p13/21 (six cases), 7q32/34 (five cases), 2p16/21 and 19p13 (four cases each), 4q25/28, 6q15/21 and 12q22/23 (three cases each). In two cases, a translocation between band 19q13 and band 14q11 or 14q32 was found. This finding may indicate that an unknown oncogene in 19p13 is activated by juxtaposition next to a T-cell receptor or immunoglobulin gene in 14q11 or 14q32, respectively. In eight cases each, total or partial monosomy 4 or 6 was present suggesting that tumor suppressor genes in 4q or 6q play a role in tumor development in Hodgkin's disease. Moreover, the aberrant clones lacked the Y-chromosome in men and the second X-chromosome in women in eight out of nine and in two out of three cases, respectively. Although different cell populations, especially T cells, showed mitotic activity in unstimulated short term culture, combined immunophenotyping and karyotyping unequivocally demonstrated that CD30 and CD15 positive Hodgkin and Sternberg-Reed cells represented the chromosomally aberrant clones.

Adult↗
PubMed1993

Rationalization of in situ hybridization: testing up to 16 different probes on a single slide.

Although particularly interested in tumor research, investigators in many tumor cytogenetics laboratories cannot afford extensive molecular/interphase cytogenetics studies in addition to routine cytogenetics analyses, primarily because many slides must be stained to examine a few cases using a panel of centromeric probes. Moreover, fluorescence in situ hybridization (FISH) techniques mostly require freshly prepared reagents, such as hybridization mixtures or antibody solutions. These technical requirements are very time-consuming, thus limiting their use in routine screening. We report a significantly economical method for rapid performance of interphase cytogenetics in great numbers of cases. The major advantage if its superior efficiency: up to 16 different probes may be used on one single slide. Moreover, the method is significantly cheaper than other techniques owing to minimal probe consumption. The technique is also best suited if great numbers of new probes, e.g., polymerase chain reaction (PCR)-generated YAC-probes, must be tested for their applicability in FISH.

Chromosomes, Human, Pair 1↗