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Biomedical subjects

B de Jong

Publications and source records attributed to B de Jong.

At least 91 records · Page 5Linked to original sources

DNA ploidy and karyotype in recurrent and metastatic soft tissue sarcomas.

To study mechanisms involved in evolution of soft tissue sarcomas, we compared DNA ploidy and karyotypes at different stages of their disease in two patients with myxoid liposarcomas (MLS), one with a fibrosarcoma (FS), and two with rhabdomyosarcomas (RMS). None of the MLS samples revealed clearcut histologic changes in later samples as compared to their primaries, and the DNA ploidy in all samples was diploid. In one patient karyotypes at four different times during the 19 yr of his disease all revealed a t(11;12) (p15;q13), but additional clonal chromosomal abnormalities occurred only in later recurrences. In another patient the karyotypes obtained in the 26th and 28th yr of his disease were similar and included the t(12;16) (q13;p11), characteristic of MLS. A comparison with karyotypes of six other MLS patients at different disease stages suggests that the presence of a t(12;16) may correlate with less aggressive clinical behavior. The histology of the FS remained low-grade and the DNA ploidy diploid. The karyotype, however, showed evolution. In both MLS and FS, chromosomal changes thus seem to be a more sensitive marker for tumor progression than histologic changes or DNA ploidy. In one embryonal RMS, karyotypes obtained 7 and 11 yr after the primary diagnosis were different but clearly had a common "progenitor." In one alveolar RMS, the primary and the synchronous lung and lymph node metastases all revealed a t(2;13). The findings in RMS suggest that polyploidization is an early event in tumor evolution, especially in the alveolar subtype, which may be followed by additional chromosomal changes. In addition, DNA ploidy was measured in eight other RMSs. Among the RMSs the embryonal subtype was characterized by DNA aneuploidy, whereas three of the alveolar cases were in the tetraploid range and one was peridiploid. In local recurrences and in metastases changes in DNA index were observed in half the cases.

Adolescent↗

Mediastinal germ cell tumor with secondary nongerm cell malignancy, and extensive hematopoietic activity. Pathology, DNA-ploidy, and karyotyping.

We report on a malignant germ cell tumor located in the anterior mediastinum. After chemotherapy the tumor was classified as residual teratoma with sarcomatous components. There was extensive hematopoiesis in the tumor tissue. The tumor cells had a modal chromosome number of 76; the only structural abnormality was a deletion of the long arm of chromosome 9. An i(12p) chromosome was lacking in this tumor. Karyotyping of peripheral blood and bone marrow occasionally showed metaphases with numerical and structural abnormalities, probably related to chemotherapy. The patient died within two years after the initial diagnosis, of a poorly differentiated hematopoietic malignancy, probably of myelomonocytic origin, based on morphology and the fact that non-specific esterase activity was demonstrated in the tumor cells. The karyotype of this malignancy was highly abnormal, but unrelated to that of the mediastinal malignant GCT. In this case there is no proof that the secondary malignancy was derived from the primary mediastinal malignant GCT. In view of the multiple aneuploid stem lines in the primary tumor, this possibility cannot be dismissed either.

Adult↗

Partial 3q duplication syndrome and assignment of D3S5 to 3q25-3q28.

We report a girl with a de novo duplication of the distal part of the long arm of chromosome 3 and review the literature. Our patient had the facial characteristics and many other anomalies of the partial 3q duplication syndrome. As a hitherto undescribed symptom in partial 3q trisomy syndrome, she had microphthalmia. The karyotype of this girl was interpreted as an inverse duplication of the terminal portion of chromosome 3: 46,XX,inv dup (3)(pter-q28::q28-q25::q28-qter). Quantitative hybridisation studies with 3p and 3q probes gave a consistent 3:2 ratio of the relative intensities of the q bands in relation to the p bands between patient and control. This confirmed the presence of a 3q duplication and delineated the location of D3S5 to 3q25-3q28.

Blotting, Southern↗

Cytogenetic study of a nodular hyperplasia of the thyroid after irradiation for Hodgkin's disease.

We describe cytogenetics of a case of nodular hyperplasia of the thyroid with papillary microcarcinoma following radiotherapy for Hodgkin's disease. The chromosomal pattern found was very heterogeneous with a clonal abnormality of chromosome 10, among others. Together with some recent data from the literature, this finding may point to an important role of chromosome 10 abnormalities in the pathogenesis of benign and malignant thyroid neoplasms.

Adult↗

A 46,XY female with mixed gonadal dysgenesis and a 48,XY, +7, +i(12p) chromosome pattern in a primary gonadal tumor.

Cytogenetic analysis of a primary germ-cell tumor originating from the streak gonad of a 20-year-old phenotypic female with a 46,XY karyotype and mixed gonadal dysgenesis revealed a 48,XY, +7, +i(12p) chromosomal pattern. Germ-cell tumors originating from gonads of normal males are usually highly aneuploid. An isochromosome 12p as well as an overrepresentation of chromosome 7 material are among the specific changes most consistently observed. The present case shows that tumors of dysgenetic gonads, albeit being near-diploid, may exhibit similar chromosomal changes. This observation lends additional support to the hypothesis that these specific cytogenetic anomalies may play an important role in the pathogenesis of human germ-cell tumors.

Adult↗

Demonstration of the genuine iso-12p character of the standard marker chromosome of testicular germ cell tumors and identification of further chromosome 12 aberrations by competitive in situ hybridization.

The recently developed competitive in situ hybridization (CISH) strategy was applied to the analysis of chromosome 12 aberrations in testicular germ cell tumors (TGCTs). DNAs from two rodent-human somatic cell hybrids, containing either a normal chromosome 12 or the p arm of chromosome 12 as their unique human material, were used as probes. Our results demonstrate a genuine iso-12p character of the standard marker chromosome in TGCTs. Moreover, variant markers were identified representing translocation products that also involve chromosome 12.

Chromosome Aberrations↗

Dual parameter flow cytometry for deoxyribonucleic acid and intermediate filament proteins of residual mature teratoma. All tumor cells are aneuploid.

Most testicular germ cell tumors of adults are presumably derived from polyploid carcinoma in situ. Thus, one would expect that even highly differentiated teratoma components are aneuploid and that it is unlikely to find diploid tumor cell (sub)populations. We studied 10 residual mature teratomas (RMTs) using a dual parameter flow cytometry procedure. Nuclear DNA was stained with propidium iodide and cytoplasmic intermediate filament proteins, in particular, cytokeratins, with fluorescein isothiocyanate-labeled specific monoclonal antibodies. Cells in RMTs, immunoreactive with antibodies to cytokeratins were considered to be tumor cells. These were always found to be aneuploid, in agreement with the available cytogenetic data on these tumors. The diploid cells present in RMTs were devoid of cytokeratins; therefore, these cells represent the nonmalignant normal host stromal and inflammatory cells. These results, in accordance with our earlier finding, indicate that diploid testicular germ cell tumors are extremely rare in adults, and that even the histologically benign somatic tissues in RMT after polychemotherapy are aneuploid.

Adult↗

Cytogenetics of three cases of ANLL M2 and M4. Involvement of chromosomal region 8q22 in all three but 21q22 in only one.

Cytogenetic investigation of the bone marrow of two patients with acute nonlymphocytic leukemia (ANLL), French-American-British Cooperative group (FAB) classification M2, revealed a translocation (8;22)(q22.1;q13.3), without involving chromosome 21, and a variant translocation (8;21)(q22;q22). These findings, together with a del(8)(q22) found in a patient with refractory anemia, erythroblastic (RAEB)-t with progression to acute myelogenous leukemia (AML)-M4, are discussed in relation to the possible role of abnormalities of chromosomes 8 and 21 in the oncogenesis of ANLL M2 and M4.

Child, Preschool↗

Cytogenetic analysis of murine embryo-derived tumors.

The possible relationship among malignancy, differentiation, and chromosomal constitution of primary embryo-derived tumors was studied. Tumors were induced by transplanting 7-day-old mouse embryos under the kidney capsule of syngeneic BALB/c recipients. Transplantation of 101 embryos resulted in 18 tumor-bearing mice: 36 teratocarcinomas; 18 teratomas; and 27 yolk sac tumors. Some of the yolk sac tumors proved to be retransplantable for several generations. Cytogenetic investigation of the primary embryo-derived tumors revealed that the majority of teratocarcinomas (82%) were chromosomally normal, whereas almost all (83%) karyotyped teratomas and yolk sac tumors had a highly abnormal chromosomal constitution. Most common aberrations were polyploidy; overrepresentation of chromosome 1, 6, 15, or 19; and an underrepresentation of chromosome 2, 4, 14, or a sex chromosome.

Animals↗

Yolk-sac carcinoma develops spontaneously as a late occurrence in slow-growing teratoid tumors produced from transplanted 7-day mouse embryos.

Seven-day embryos of BALB/c mice transplanted underneath the kidney capsule of adult syngeneic recipients form either benign teratomas or teratocarcinomas, which can be distinguished from one another histologically at 8 weeks post-embryonic transplantation. Embryo-derived (ED) teratomas were allowed to remain in the host for an additional period up to 1 year after embryo transplantation, to test their malignant potential. It was found that a considerable number of slow-growing small tumors derived from embryonic transplant give rise to parietal yolk-sac carcinomas. A proportion of these tumors contained foci of visceral yolk-sac and trophoblastic differentiation, which gradually disappeared in successive transplantations. We conclude that parietal yolk-sac carcinoma develops as a late event in some ED teratomas. These malignant tumors originate either from small foci of yolk sac originally included in the grafted embryo or, more likely, from the yolk sac formed from the differentiating embryonic stem cells.

Animals↗

Chromosomal damage in peripheral blood lymphocytes of patients treated for testicular cancer.

We describe the presence of a large number of chromosome aberrations in lymphocytes of 50 patients with testicular cancer. These chromosomal aberrations were not only found in patients treated with chemotherapy but also in untreated patients or in patients after surgery alone. Our results suggest a role for genetic instability in the pathogenesis of testicular cancer. This instability might be a risk factor for the development of secondary malignancies.

Adult↗

Cytogenetics of carcinoma in situ of the testis.

Carcinoma in situ (CIS) of the testis is the precursor lesion of most testicular germ cell tumors (TGCTs). Karyotyping of CIS is important for a better understanding of the pathogenesis of TGCTs and the progression to invasive cancer. We karyotyped three cases of CIS. All three cases showed a numerical abnormal chromosomal pattern. In one case, two copies of the germ cell tumor marker i(12p) were found.

Adult↗

Cytogenetics of thyroid follicular adenomas.

We present the results of a cytogenetic study of three cases of follicular adenoma of the thyroid. All three cases had a numerical strongly abnormal karyotype with most abnormalities (eg, +4 or +5, +7, +9, +12, +16) in common, possibly indicating that this cluster of abnormalities might be specific for follicular adenomas. For benign tumors, the three cases showed a remarkably abnormal karyotype. These cases are another example of benign tumors with chromosomal abnormalities that might be specific for follicular adenomas.

Adenoma↗

Karyotyping and DNA flow cytometry of metastatic ovarian yolk sac tumor.

We karyotyped a metastasis composed of pure yolk sac tumor derived from a primary ovarian germ cell tumor with two components: a dermoid cyst [DNA index (DI) 1.0] and a pure yolk sac tumor (DI 1.88). The metastatic yolk sac tumor had a hypertriploid karyotype and a DI of 1.78 and lacked the germ cell tumor marker i(12p). The absence of this marker in a metastasis from a tumor with a dermoid cyst component might be indicative for a pathogenesis of the yolk sac tumor similar to that of a dermoid cyst and different from that of dysgerminoma.

Adult↗