Salmonella in alfalfa sprouts.
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Publications and source records attributed to B de Jong.
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Two malignant extragonadal germ cell tumors are reported, histologically classified as immature teratomas, having pseudodiploid karyotypes with complex structural rearrangements but lacking isochromosome 12p or other rearrangements involving 12p. The absence of 12p material in structural rearrangements was confirmed by chromosome painting. In the two tumors the following common chromosomal breakpoints were found: 6p21, 6p22, 6q23, and 11q13. Exactly the same chromosomal regions, 6p22::6q23 and 6p21::11q13, were involved in fusions. The two tumors belong to a new entity of extragonadal immature teratomas of adults which may be located in the retroperitoneum and posterior mediastinum and are prone to blood borne metastasis.
Several human renal cell carcinomas with X;autosome translocations have been reported in recent years. The t(X;1)(p11.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translocation form a distinct subgroup of RCC. Here we report two new cases, one with a t(X;10)(p11.2;q23), the other with a t(X;1)(p11.2;p34). The common breakpoint in Xp11.2 suggests that they belong to the above-mentioned subset of RCC. Using FISH in conjunction with X-specific YAC clones, we demonstrate that the two new cases exhibited distinct breakpoints within Xp11.2.
Malignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto-oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in 102 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i(12p) are higher in NS than in SE. This may suggest that i(12p) is involved in tumor progression. Besides i(12p), several clonal structural chromosomal abnormalities were found, but none appeared to be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome numbers of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT.
We report two cases of apparently balanced complex de novo chromosomal rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation, respectively. Chromosomes were studied using GTG-banding and fluorescent in situ hybridization (FISH). In one case four chromosomes and in the other case three chromosomes were involved in the rearrangements. One of the pregnancies was terminated and no external or internal showed no abnormalities. The child is now 3 years old and has neither congenital anomalies nor evidence of delayed psychomotor development.
Many of the reported oncocytomas have different chromosome abnormalities, indicating that they comprise a cytogenetically heterogenous group of tumors consisting of potentially cytogenetic subgroups. We have performed cytogenetic studies on nine renal oncocytomas. Clonal abnormalities were present in eight tumors. The findings most observed were the loss of the Y chromosome, and abnormalities of chromosomes 1 and 22. We also observed telomeric associations (tas) in two tumors and structural aberrations of chromosomes 9p and 19q, as well as monosomy 10. In two cases we found a similar reciprocal t(5;11)(q35;q13) in two cases. Review of the literature disclosed one other oncocytoma with a t(5;11) (q35;q13). This suggests that t(5;11)(q35;q13) defines a (second) subset of oncocytomas apart from the subgroup specifically associated with the loss of chromosomes 1 and Y.
Chromosome aberrations were studied in short-term cultures of non-neoplastic renal tissue and tumor tissue in 60 patients, 41 male and 19 female, with renal cell cancer (RCC), and in normal renal parenchyma from two cases, one male and one female, at autopsy with non-kidney related disease. Cytogenetic analysis of the non-neoplastic renal tissue from the patents with RCC revealed clonal chromosome aberrations in 32 of 60 (53%) cases: -Y, +Y, +X, +5, +7, +10, +12, +13, +18, +21, and del(9)(q12). In all other cases, non-clonal numerical and structural chromosome aberrations were observed, except for three cases of culture failure. Forty-two cases of RCC yielded clonal chromosomal abnormalities. Trisomy 7 was present in 23 cases, loss of Y in 14, trisomy 5 and 12 in three, trisomy 18 in two cases, and trisomy 10 in one case. Clonal chromosomal anomalies found in two cases from kidneys without neoplasia were trisomy 7, trisomy 12, and trisomy 18 in one case, and monosomy of chromosome 15 in the other. The proportion of aberrant cells in both cases (with clonal and non-clonal aberrations) was, on average, 24%. Apparently, chromosomal abnormalities only play a role in the process of oncogenesis when they are in the appropriate stage and lineage of differentiation.
We report on a 12 year old mentally retarded boy who presented at birth with bilateral knee dislocations, dislocation of the right hip, and general joint laxity. Cytogenetic studies showed a 49,XXXXY karyotype. Hyperlaxity of joints is known to occur in 49,XXXXY patients, but congenital knee dislocation has not been reported. Rarely in 49,XXXXY and 49,XXXXX syndromes Larsen-like features may be seen. Patients with congenital joint dislocation or laxity, combined with other malformations, especially if psychomotor development is delayed, should be karyotyped to exclude chromosomal abnormalities.
We report the chromosomal characteristics of a recurrent pineal non-seminomatous germ cell tumor in a 16-year-old male patient. This non-seminomatous tumor had the following components: embryonal carcinoma, teratoma, yolk sac tumor, and trophoblastic giant cells. Chromosome analysis showed a near-triploid karyotype (64 chromosomes), including two copies of an isochromosome 12p. This latter finding could be confirmed using 12p-specific competitive in situ hybridization techniques applied to cultured cells (T2219-P6 cell line) derived from the tumor. The present findings are in keeping with the hypothesis that isochromosome 12p formation is associated with the development of malignant extragonadal germ cell tumors.
The initial cytogenetic analysis of a biphasic synovial sarcoma revealed complex anomalies involving six different chromosomes: 46,Y,t(X;18;5;4)(p11;q11;p13;q12),t(2;5)(q35;q11). After fluorescence in situ hybridization (FISH) analysis, using chromosome X-specific plasmid library and YAC probes, the situation appeared to be even more complex, with an insertion of part of the X chromosome short arm into the der(5)t(5;18). In spite of these complex chromosomal rearrangements, the Xp11 breakpoint could be mapped to within the ornithine aminotransferase (OAT)L1 cluster, very similar to that reported previously for the standard t(X;18)(p11;q11) in synovial sarcomas. These findings suggest common pathogenetic pathways in these cytogenetically different but morphologically similar tumors.
Nonepithelial malignant renal tumors are very rare, comprising approximately 2-3% of all malignant renal tumors. We were able to culture and subsequently karyotype a leiomyosarcoma (LMS) of the kidney that showed the following representative karyotype: 84,XY,add(X)(q25),-Y,add(1)(p11),dic(1;20) (p34;q13.3),-5,-6,dup(6)(q24),i(7)(p10),add(8)(p11),-9,-11,add(13)(p11), -15,-15 , add(17)(q24)x2,-18,-19,-21,-22,-22, +mar1(?hsr),+mar2,+2mar. A clonal add(1)(q11) was also evident. The DNA index was 1.9. Our results as compared with data from the literature suggest that LMS of the kidney has most cytogenetic aberrations reported to be characteristic of LMS, especially those located in the abdomen, and that different genetic mechanisms of initiation and progression appear to play a role in LMS of similar histology but from different anatomic sites.
The molecular characterization of a recurring complex chromosomal translocation involving 6p21, 6p22, 6q23, and 11q13 in two independent but similar extragonadal human germ cell tumors was initiated using fluorescence in situ hybridization (FISH) and pulse field gel electrophoresis (PFGE) techniques. By using a series of specific probes from the 11q13 region, the translocation breakpoint in this chromosomal band could be located within a long-range restriction enzyme map in between the markers D11S457 and D11S546. In addition, aberrantly hybridizing restriction fragments were revealed by PFGE in both tumors, indicating that the breakpoint region must be located within a distance of at maximum 200 kilobase pairs (kbp) from the nearest DNA marker (D11S546).
Chondrosarcomas are a heterogeneous group of bone neoplasms of which the basic neoplastic tissue is cartilaginous. Frequently the histologic diagnosis and grading of chondrosarcomas is difficult and the histologic appearance does not always reflect the biologic behavior of these tumors. Therefore, it is important to find other parameters that can be of help in the proper diagnosing and grading of these neoplasms. To this end, we attempted to correlate the chromosomal pattern of chondrosarcomas to their histologic subtypes and grades. The cytogenetic analysis of two intermediate-grade chondrosarcomas of bone, and a review of the literature, are presented.
Radiotherapy patterns were determined in all 34,487 cancer patients diagnosed between 1975 and 1989 in south-eastern Netherlands, a densely populated and prosperous area with a greying population of almost 1 million inhabitants. Specialised care was available in 10 community hospitals with expanding staffs and in a non-academic radiotherapy centre, the distance never exceeding 50 km. With respect to western Europe the cancer incidence rates for this area were relatively high for males and average for females during this period. We computed overall and tumour-specific percentages of patients receiving radiotherapy as primary treatment (RT1a) and estimated this for initial treatment of recurrence or metastasis (RT1b). The total number of patients receiving RT1a increased by about 2% per year, but age-adjusted figures remained stable at 36% for females and increased from 28% to 32% for males. Since 1986 about 40% of all new cases receive RT1a and RT1b and about 40% of all RT1a undergo secondary radiotherapy for recurrence or metastasis. Of all male and female patients 70% and 50%, respectively, were over 60. Diverse underlying tumour-specific trends in RT1a were observed: children and adolescents with cancer received RT1a less often (25% vs. 40%) as did patients with cervical (55% vs. 80%), ovarian (9% vs. 17%), small cell lung (25% vs. 55%) and non-melanoma skin cancer (5% vs. 55%); patients with stage 1 breast (70% vs. 45%), rectal (30% vs. 10%) and prostate cancer (31% vs 13%) and adenocarcinoma of the lung (40% vs. 20%) received RT1a more often.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Recently we have shown, by combining in situ hybridization and immunohistochemistry, that carcinoma in situ (CIS) adjacent to seminoma (CIS/SE), like SE, usually contains three copies of the centromeric region of chromosome 15/tumor cell. In contrast, CIS adjacent to nonseminomatous testicular germ cell tumors of adults (CIS/NS), as well as NS itself, have two copies. EXPERIMENTAL DESIGN: In the present study we have used this approach to investigate the clonal origin of the SE and NS components of combined tumors (CTs). We counted the number of copies of chromosome 15 centromeric regions in tumor cell nuclei of the CIS, SE, and NS components of nine CTs. RESULTS: We show that the number of copies of centromeric regions of chromosome 15 in both the SE and the NS component, and the adjacent CIS of the same CT, may be high (SE-pattern) or low (NS-pattern). In two cases, the copy numbers were high in the SE component and its adjacent CIS, and low in the NS component and its adjacent CIS. CONCLUSIONS: The data suggest that in most CTs the SE and the NS components have a monoclonal origin, and that karyotype evolution in CIS and the invasive tumor is very similar.
BACKGROUND: Both DNA flow cytometry and cytogenetic analysis have been used to study soft tissue tumors. With flow cytometry, the DNA content of a relatively large number of cells can be examined, but cytogenetic analysis gives more detailed information about genomic changes. EXPERIMENTAL DESIGN: In order to compare the advantages and drawbacks of DNA flow cytometry versus chromosomal analysis, 92 primary or recurrent malignant, 16 borderline malignant, and 13 benign soft tissue tumors were karyotyped after short-term culture. DNA ploidy was determined by flow cytometry of suspensions prepared from frozen or paraffin-embedded samples. From 97 patients, 121 samples were analyzed. RESULTS: On the basis of the results, four groups were distinguished: DNA-euploid tumors with normal diploid karyotypes (group a) or with abnormal (group b) karyotypes, and DNA-aneuploid tumors with normal (group c) or abnormal (group d) karyotypes. The findings in group b show that structural chromosomal abnormalities or minor numerical aberrations of chromosomes are not detected by DNA flow cytometry. In group c, the finding of tumors with an aneuploid DNA-profile and cells with normal karyotypes is most likely due to overgrowth of fibroblasts during culture and subsequent karyotyping of normal cells. CONCLUSIONS: The findings show that a) DNA flow cytometry has a higher success rate than karyotyping, b) both techniques are complementary, such that DNA flow cytometry gives an "overview", whereas karyotyping gives more detailed information; comparison of both techniques in individual cases leads to a better understanding of the chromosomal events that occurred during oncogenesis, c) histologically low grade tumors are generally DNA-diploid, but may have an abnormal karyotype, and d) histologically high-grade sarcomas tend to have an aneuploid DNA-profile; they are generally more difficult to karyotype.
In the embryonal carcinoma cell line Tera and its 3.7-fold cis-diamminedichloroplatinum(II) (CDDP)-resistant subline, Tera-CP, parameters were studied that might have changed in relation to induction of CDDP resistance. Phenotypes of both lines were embryonal carcinoma. Karyotypes were related with a decreased mean number of chromosomes and fewer copies of the short arm of chromosome 12 in Tera-CP. Tera-CP showed cross-resistance for melphalan and 4-hydroperoxycyclophosphamide and had an 1.4-fold increased glutathione (GSH) level, a 1.5-fold increased glutathione S-transferase (GST) activity, and a 1.4-fold increased GST pi expression compared to Tera. Tera-CP was cross-resistant to 5-fluorouracil, but thymidylate synthase activity was not increased. Topoisomerase I and II activities and c-myc RNA and protein expression were the same in both lines. Platinum accumulation was equal in both lines, and platinum-DNA binding was lower in Tera-CP than in Tera. Both cell lines were xenografted into nude mice and tumors showed marked differentiation. Tera-CP tumors were 2.8-fold resistant to CDDP compared to Tera tumors. In new cell lines derived from xenografts of Tera and Tera-CP CDDP sensitivity, GST activity and GSH level corresponded with their sensitivity and resistant origin. Tera-CP is a model of in vitro and in vivo CDDP resistance with the GSH/GST detoxifying system as an important mechanism. CDDP resistance could be induced without a concomitant increase in differentiation.
Human testicular germ-cell tumors (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumors are characterized by the presence of a highly specific chromosomal abnormality, i.e., an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome is found in more than 80% of TGCTs. Isochromosome 12p has also been observed in some ovarian and extragonadal germ cell tumors. In the remaining so-called i(12p)-negative TGCTs other abnormalities involving chromosome 12, mainly 12p, can be found. In order to establish whether 12p abnormalities other than i(12p) are a common phenomenon in TGCTs, a panel of 11 i(12p)-negative tumors was investigated using multicolor fluorescence in situ hybridization. All TGCTs examined appeared to contain chromosomal abnormalities involving 12p, resulting in a distinct overrepresentation of short arm sequences. In addition, indications were obtained for a clonal evolution in one of the tumors. Our data suggest that the occurrence of 12p abnormalities is a common phenomenon in i(12p)-negative TGCTs and that these abnormalities, analogous to i(12p), may contribute to the process of tumor development.