bluuebunny/crossref_metadata_2025 huggingface dataset:
Outgrowth of Stable Class I Major Histocompatibility Complex‐Expressing Subsets From Immunogenic Variants of a Murine Mammary Carcinoma: Association with a Differentially Staining Region on Chromosome 9
Authors: Elliott Bruce E. , Xu Wei , Brissette Louise , Deeley Roger G. , Mudrik Kevin , Marshall John , Vekemans Michel , Holden Jeanette J. A.
Published: February 2007

We have examined interactions among intratumor subpopulations during the rejection of immunogenic variants of a murine mammary carcinoma (SPI) and in the outgrowth of tumorigenic “revertant” subsets. Analysis of subclones isolated during the early phase of rejection of one immunogenic variant revealed extensive cellular heterogeneity of tumor‐forming ability and class I major histocompatibility complex (MHC) expression. Two main categories of subclones were identified. One set expressed high levels of class I MHC (MHC H) and grew poorly or not at all in normal syngeneic mice. The second set of clones expressed generally low levels of class I MHC (MHCL) and exhibited progressive growth in vivo, similar to the parent tumor. The steady‐state mRNA levels for class I MHC and β2‐microglobulin were constitutively elevated in MHCH clones compared to MHC L clones or the parent tumor. However, in vivo tumorigenic outgrowths from immunogenic variants always expressed the MHCH phenotype. A cytogenetic analysis was carried out to determine the clonal origin and lineage relationship of in vivo selected tumor outgrowths. Surprisingly, tumor outgrowths from mixtures of karyotypically distinct MHCH and MHCL subclones were derived from one lineage within the MHCH subset, despite the fact that MHCH subclones exhibited slower growth in vivo than MHCL subsets when analyzed individually. These results suggest that in polyclonal populations the various subsets sometimes interact in a way that overrides the influence of immunogenic and MHC phenotypes of individual subclones.
Variant Translocations of Chromosome 13 in Alveolar Rhabdomyosarcoma
Authors: Douglass Edwin C. , Rowe Susan T. , Valentine Marc , Parham David M. , Berkow Roger , Paul Bowman W. , Maurer Harold M.
Published: February 2007

In three cases of alveolar rhabdomyosarcoma with variant translocations, two tumors contained an identical translocation, t(1;13)(p36.1;q14); the third tumor contained a t(8;13)(p21;q14). All three patients were 2 years old, markedly younger than the median age for patients with t(2; 13)‐positive alveolar rhabdomyosarcoma. The alteration of genetic material on chromosome 13 may be of primary importance in the development of alveolar rhabdomyosarcoma.
Chromosomal Translocation t(1;13)(p36;q14) in a Case of Rhabdomyosarcoma
Authors: Biegel Jaclyn A. , Meek Rita S. , Parmiter Annette H. , Conard Katrina , Emanuel Beverly S.
Published: February 2007

Cytogenetic studies of a rhabdomyosarcoma of mixed embryonal and alveolar histology in an II ‐month‐old male revealed a single structural abnormality, t(1;13)(p36;q14). This abnormality may define a subset of patients with a variant of the t(2;13)(q35;q14) translocation frequently seen in alveolar rhabdomyosarcoma.
A complex genetic rearrangement in a t(10;14)(q24;q11) associated with T‐cell acute lymphoblastic leukemia
Authors: Park James K. , Le Beau Michelle M. , Rowley Janet D. , Diaz Manuel O. , Shows Thomas B.
Published: February 2007

The t(10;14)(q24;q11) is observed in the leukemia cells of 5–10% of cases of T‐cell acute lymphoblastic leukemia (T‐ALL). Recently, molecular analyses of a number of these translocations revealed simple reciprocal translocations between the T‐cell receptor delta chain gene (TCRD) and a region of 10q24. We have characterized, at the molecular level, a t(10;14)(q24;q11) in a patient with T‐ALL. The translocation in this case, in contrast to the previous cases, is part of a complex genetic rearrangement. In addition to a reciprocal translocation between the Dδ3 gene segment of TCRD and a region of 10q24, a local inversion occurred within TCRD, involving the Dδ2 and Vδ2 gene segments. As a consequence, the entire joining and constant regions and most of the diversity regions of TCRD are located on the derivative 14 chromosome, whereas the joining and constant regions of TCRA are positioned on the derivative 10 chromosome. The chromosome 10 breakpoint in our patient, as in other t(10;14), clusters within a 9 kb breakpoint region. The occurrence of seven breakpoints within a localized region of chromosome 10 implies the existence of a nearby gene whose activation may have conferred a selective advantage on the leukemia cells. Moreover, as in the previous cases, the translocation in the present study exhibits recombination signal sequences or signal‐like sequences adjacent to the breakpoint junction. The presence of such motifs suggests the involvement of the recombinase enzyme system in the generation of this genetic alteration.
Ring chromosomes in a retroperitoneal lipoma of childhood
Authors: Mitchell Erika L. D. , Kelsey Anna , Armstrong Gordon , Dickson Alan
Published: February 2007

We report here the presence of ring chromosomes in a retroperitoneal lipoma from a 12‐year‐old male. Ring chromosomes are strongly associated with the pathological subtype “atypical lipoma” in adults. In contrast, however, the tumour described here possesses no atypical features.
Ph‐positive chronic myeloid leukemia with loss of the segment distal to M‐bcr
Authors: Pedersen Bent , Bartram Claus R. , Nielsen Johan Lanng
Published: February 2007

We describe a patient with chronic myeloid leukemia (CML) and a 22q‐ but no 9q + chromosome. Southern blot analysis showed a BCR rearrangement. The patient soon developed profound and superficial thrombophlebitis in arms and legs and died from pulmonary embolisation 15 days after diagnosis. Five CML cases with a deletion of 22q but no known translocation of 22qll → qter have been described earlier. The present patient is the first such case, however, in whom a BCR rearrangement has been demonstrated.
Nonradioactive in situ hybridisation of the translocation t(1;7) in myeloid malignancies
Authors: Kibbelaar Robert E. , Mulder Jan‐Willem R. , Dreef Enno J. , Kluin Philip M. , Kamp Harmen Van , Haak Hans L. , Raap Anton K. , Wessels Hans W. , Beverstock Geoffrey C.
Published: February 2007

Bone marrow cells of four patients with t(1;7) and myelodysplasia or acute myeloid leukemia were analyzed using nonradioactive in situ hybridisation. As probes, centromeric alphoid DNA sequences of chromosomes 1 and 7, a satellite DNA probe for 1q12, and chromosomespecific libraries of chromosomes 1 and 7 were used. The breakpoints of the t(1;7)(p11;p11) as determined by banding analysis could be studied more accurately, and the recently proposed designation t(1;7)(cen;cen) was confirmed in all four cases. Colocalization of alphoid DNA sequences of chromosomes 1 and 7 by double target in situ hybridisation was demonstrated in metaphase cells and also in interphase nuclei. The in situ hybridisation method described is applicable for the screening of peripheral blood cells or archival material.
Chromosomal in situ suppression hybridization of immunologically classified mitotic cells in hematologic malignancies
Authors: Tiainen Marianne , Knuutila Sakari , Popp Susanne , Emmerich Patricia , Cremer Thomas , Parlier Valerie , Bellomo Martine Jotterand , Ruutu Tapani
Published: February 2007

Chromosomal in situ suppression (CISS) hybridization was performed with library DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically stained bone marrow cells of four patients with a hematologic neoplasm, including two patients with myelodysplastic syndrome and trisomy 8, one patient with promyelocytic leukemia bearing the translocation t(15;17)(q22;q11–12), and one patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In all patients, the results of conventional karyotype analysis could be confirmed by one‐ or two‐color CISS hybridization using the appropriate chromosome‐specific libraries. Our results show that CISS hybridization can detect both numerical and structural chromosome changes in immunologically classified cells with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analyses is a decisive advantage of this approach. In addition, the suitability of this approach for interphase cytogenetics is discussed.
t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma
Authors: Griffin Constance A. , Zehnbauer Barbara A. , Ambinder Richard , Beschorner William E. , Mann Risa
Published: February 2007

We have identified two cases of previously untreated, small lymphocytic lymphoma with extranodal involvement, which had a reciprocal translocation, t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are remarkably similar to two previously reported cases carrying this translocation with regard to clinical features, cytogenetic abnormality, histologic subtype, and immunophenotype. Molecular genetic analysis of these two cases revealed clonal gene rearrangement of the IGH locus but only germline configuration of the BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2 rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement appear to make up a phenotypically identifiable subgroup. Identification of the genes at the translocation breakpoints will be important.
A synovial sarcoma with t(x;18)(p11;q11) in a patient with turner's syndrome
Authors: Miozzo Monica , Sozzi Gabriella , Cariani Claudia T. , Pierotti Marco A. , Porta Gluseppe Della , Palma Silvana Di , Luksch Roberto , Azzarelli Alberto
Published: February 2007

The first case of synovial sarcoma in a patient with Turner's syndrome (45,X) is reported. Cytogenetic analysis of the tumor cells showed that the only X chromosome was involved in the t(X;18)(p11;q11) characteristic of synovial sarcoma.
The translocation (1;14)(p34;q11) in human t‐cell leukemia: Chromosome breakage 25 kilobase pairs downstream of the tal1 protooncogene
Authors: Xia Ying , Brown Lamorna , Tsan Julia Tsou , Chuan‐Yang Cary Ying , Baer Richard , Siciliano Michael J. , Crist William M. , Carroll Andrew J.
Published: February 2007

Nearly 30 percent of patients with T‐cell acute lymphoblastic leukemia (T‐ALL) exhibit a tumor‐specific rearrangement of the TAL1 gene (also called TCL5 or SCL). These rearrangements are generated by either local DNA deletion or a (1;14)(p34;q11) chromosome translocation, and they typically result in structural alterations of the TAL1 transcription unit. In this report we present a molecular characterization of the t(1;14)(p34;q11) from a T‐ALL patient. As a consequence of the translocation, TAL1 is transposed from its normal position on chromosome 1 into the T‐cell receptor α/δ chain locus on chromosome 14. Unlike previous cases, the chromosome 1 breakpoint in this patient did not disrupt the continuity of the TAL1 transcription unit, but instead occurred approximately 25 kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant alteration of TAL1 can be mediated by long‐range cis‐activating mechanisms that are triggered by DNA rearrangement at a distant site.
Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia
Authors: Lorber Briana J. , Freeman Sallie B. , Hassold Terry , Ragab Abdel H. , Vega Roger A. , Cockwell Annette E. , Jacobs Patricia A. , Radford Martin , Doyle John , Dubé Ian D. , Zipursky Alvin
Published: February 2007

We recently began a cytogenetic and molecular study of nondisjunction in leukemic Down syndrome individuals to determine whether the mechanism by which the extra chromosome 21 originates predisposes the individual to leukemia. In the present report, we summarize our observations on 18 patients with trisomy 21 and acute or transient leukemia, including 11 patients with acute lymphocytic leukemia, three with acute myeloid leukemia, one with B‐cell lymphoma, one with acute megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker studies of the parental origin of the extra chromosome 21 indicated that 16 of the 18 cases (89%) were maternally derived, a percentage similar to that seen among nonleukemic Down syndrome patients. We noted that most leukemic Down syndrome patients had one locus or more in which parental heterozygosity was maintained in the trisomic individual, indicating a meiotic rather than a mitotic origin for the trisomy.
Clonal structural chromosome aberrations in nonneoplastic cells of the skin and upper aerodigestive tract
Authors: Mertens Fredrik , Jin Yuesheng , Heim Sverre , Mandahl Nils , Mitelman Felix , Jonsson Nils , Persson Bertil , Wennerberg Johan , Mertens Ove , Salemark Lars
Published: February 2007

Cytogenetic analyses of tumors of the skin and upper aerodigestive tract have repeatedly revealed small, pseudodiploid clones characterized by balanced structural rearrangements and a high frequency of cells with nonclonal structural aberrations. However, the lack of common cytogenetic denominators within the different histologic subtypes, the discrepancy between cytogenetic findings and data obtained from flow cytometric DNA content studies, and the occasional identification of tumors with massively rearranged karyotypes indicate that the chromosome rearrangements present in pseudodiploid cells have little to do with the tumorigenesis or progression. Further support for this conclusion, and indirect evidence that the pseudodiploid clones probably do not represent the tumor cell populations, derives from the present study in which clonal and nonclonal structural rearrangements were also found in short‐term cultures from nonneoplastic skin and pharyngeal mucosa. It is possible that the aberrations are present in subepithelial fibroblasts that have accumulated DNA damage due to extensive exposure to potentially carcinogenic agents.
Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma
Authors: Shapiro David N. , Valentine Marc B. , Sublett Jack E. , Sinclair Anne E. , Thomas Look A. , Tereba Alan M. , Scheffer Hans , Buys Charles H. C. M.
Published: February 2007

A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)] has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the derivative chromosome 2 or the derivative chromosome 13 without a normal chromosome 13 homologue. Ten linked DNA probes known to be located within bands 13q13‐q14 were mapped relative to the breakpoint on chromosome 13, allowing localization of the breakpoint region between two loci separated by 5.5 cM. A long‐range restriction map extending approximately 2,300 kb around these loci failed to provide evidence of rearrangement. Additionally, we confirmed that the FMS‐like tyrosine kinase gene (FLT), previously localized to 13q12 by in situ hybridization, is located proximal to the breakpoint, and we demonstrated that FLT is not a target for disruption by this tumor‐specific translocation.
Frequent clonal abnormalities of chromosome band 13q 14 in b‐cell chronic lymphocytic leukemia: Multiple clones, subclones, and nonclonal alterations in 82 midwestern patients
Authors: Peterson Loann C. , Lindquist Leanna L. , Church Stephanie , Kay Neil E.
Published: February 2007

We performed cytogenetic analyses of peripheral blood lymphocytes from 82 Midwestern B‐cell chronic lymphocytic leukemia (B‐CLL) patients. The cells were cultured with mitogens for 3‐4 days. At least 15 metaphase cells were analyzed in 79 (96%) cases. Fifty (63%) of the 79 patients had clonal chromosomal alterations. Structural modifications of the long arm of chromosome 13 at or near band 13q14 were the most frequent abnormalities, identified in 23 (46%) of the patients with clonal abnormalities. In several patients, the abnormality involving band 13q14 was the sole chromosomal alteration. There was a high incidence of complex karyotypes. Nine patients had multiple subclones that appeared to result from clonal evolution; seven patients had cytogenetically unrelated clones; three patients had both subclones and cytogenetically unrelated clones. Nonclonal abnormalities were also prominent. Our study confirms the high incidence of clonal abnormalities involving chromosome arm 13q and documents the clustering of abnormalities at band 13q14 in B‐CLL. The evidence for clonal evolution and the presence of multiple unrelated clones in these patients suggest that B‐CLL may not be a karyotypically stable disease.
Karyotypic evolution of a murine mammary adenocarcinoma in vitro and during progression from primary to metastatic growth in vivo
Authors: Elliott Bruce E. , Xu Wei , Mudrik Kevin , Marshall John , Holden Jeanette J. A. , Vekemans M.
Published: February 2007

We have previously described a murine mammary tumor cell line (SP1) that metastasizes when transplanted into the mammary gland, but not when injected into the subcutaneous site. We used cytogenetic markers to assess genetic heterogeneity, and to monitor the selection and evolution of karyotypically distinct cell types during primary tumor growth and in metastases. The SPI tumor cells are hypotetraploid (mean chromosome number = 72), and have at least four karyotypically distinct cell types. We found no consistent pattern of selection of tumor cell types in primary tumors. However, metastases were derived from a cell type that was present in the corresponding primary tumor. In addition, novel, karyotypically distinct cell types also appeared in the metastatic nodules. Markers that appeared in metastases included two translocations, t(10; 18) and t(1;19). By injecting a mixture of cells from a metastatic nodule with a non‐metastatic clone into mice, we showed that the new cell types in metastases displayed a stable increased growth and metastatic potential when compared to the non‐metastatic clone, or when compared to the initial cell type from which the metastases derived. These results indicate that metastases are derived from a distinct cell type in the primary tumor, but that additional chromosome and cell evolution occurs, resulting in new cell types that are selected in metastases.
dup(12)(q13→qter) in two t(14;18)‐negative follicular b‐non‐hodgkin's lymphomas
Authors: Wlodarska Iwona , Mecucci Cristina , Vandenberghe Elisabeth , Hilliker Carl , Schoenmakers Eric , Stul Michel , Marynen Peter , Cassiman Jean‐Jacques , Berghe Herman Van Den , De Wolf‐Peeters Chris , Thomas José
Published: February 2007

Two t(14;18)‐negative follicular B‐non‐Hodgkin's lymphomas with the same chromosomal abnormality, dup(12)(q13→qter), are presented. The absence of a BCL2 gene rearrangement was confirmed by molecular studies in both cases. Instead, duplication of a 12q segment was found. Further evidence for the presence of the dup(12)(q13→qter) was found using fluorescence in situ hybridization. dup(12q) may be equivalent to the trisomy 12 originally described in B‐chronic lymphocytic leukemia. This chromosome anomaly has also been reported in B‐non‐Hodgkin's lymphomas, usually in association with other chromosome anomalies and a more aggressive tumor phenotype. Occurrence of dup(12q) in two histologically similar cases of follicular small cleaved‐cell lymphoma without a typical t(14;18), suggests that this karyotypic change may play a critical role in some cases of follicle center‐cell lymphomas.
Hyperdiploidy arising from near‐haploidy in childhood acute lymphoblastic leukemia
Authors: Onodera Norio , McCab Norah R. , Nachman James B. , Leonard Johnson F. , Le Beau Michelle M. , Rowley Janet D. , Rubin Charles M.
Published: February 2007

Acute lymphoblastic leukemia (ALL) of childhood is frequently characterized by a hyperdiploid karyotype. Typically, most of the affected chromosomes in the abnormal clone are present in three copies. We have studied two patients with hyperdiploid ALL whose leukemic cells were atypical in that all or most of the chromosomes were present in either two or four copies, raising a suspicion that the observed karyotype arose through duplication of chromosomes in a precursor cell with a near‐haploid chromosome number. Analysis of restriction fragment length polymorphisms confirmed that both cases arose from a near‐haploid cell; all informative disomic chromosomes tested had loss of heterozygosity. Furthermore, the hyperdiploid karyotypes did not arise via a perfect haploid cell with exactly 23 chromosomes, because tetrasomic chromosomes remained heterozygous. These two patients probably are classified best as near‐haploid cases, which often are observed to have a co‐existing hyperdiploid clone with a duplicated chromosome set. The distinction between typical hyperdiploidy and hyperdiploidy arising via a near‐haploid cell may be clinically important, because the prognosis for patients with a hyperdiploid karyotype is favorable in comparison to that of patients with a near‐haploid karyotype.
Loss of NF1 alleles in phaeochromocytomas from patients with type 1 neurofibromatosis
Authors: Xu W. , Mulligan L. M. , Ponder M. A. , Liu L. , Ponder B. A. J. , Smith B. A. , Mathew C. G. P.
Published: February 2007

Type 1 neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11–12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild‐type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild‐type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NF1 gene may act as a tumour suppressor.
Analysis of chromosome 12 aneuploidy in interphase cells from human male germ cell tumors by fluorescence in situ hybridization
Authors: Rodriguez Eduardo , Mathew Susan , Mukherjee Asit B. , Reuter Victor E. , Bosl George J. , Chaganti R. S. K.
Published: February 2007

The i(12p) marker chromosome has been found to be a highly nonrandom chromosome abnormality associated with germ cell tumors (GCTs). We have previously shown that a chromosome 12 centromere specific α‐satellite DNA probe detects the i(12p) by virtue of differences in the size of the signal originating from the i(12p) and normal chromosome 12 centromeres after fluorescence in situ hybridization (FISH) in metaphase and interphase cells of cultured GCT cell lines. We have now extended this analysis to 72 fresh GCT tumor biopsy specimens. Banded cytogenetic analysis was attempted on each of these tumors, 45 of which were found to be clonally abnormal. Data on i(12p) and chromosome 12 copy number obtained by FISH agreed well with those obtained by cytogenetic analysis. In addition, the FISH method made possible the detection and determination of i(12p) and the chromosome 12 copy number in cases in which conventional cytogenetic analysis was unsuccessful. We found the incidence of i(12p) in seminomas to be low (7%) compared to that in nonseminomas (75%) when tumor biopsy specimens were studied by FISH. Our results show that the FISH technique can be used reliably for detection of the diagnostically and prognostically useful i(12p) marker in GCT tumor biopsy specimens.
Pleomorphic adenoma cells vary in their susceptibility to SV40 transformation depending on the initial karyotype
Authors: Kazmierczak Bernd , Thode Brita , Bartnitzke Sabine , Bullerdiek Jörn , Schloot Werner
Published: February 2007

Chromosomal aberrations involving 8q12 or 12q13–15 characterize two cytogenetic subgroups of salivary gland pleomorphic adenomas. As the tumors of the two groups differ in their clinical and histologic characteristics, we decided to determine their susceptibility to SV40 transformation. We transfected cell cultures from 13 adenomas with aberrations involving 8q12 and from seven adenomas with involvement of 12q13–15 using an SV40 plasmid coding for the early region of the viral genome. Whereas all cultures with aberrations of 12q13–15 showed transformed foci, only 4 of the 13 cultures with 8q12 abnormalities showed foci of transformed cells. We also observed a much higher immortalization rate in the first group (3/7 vs. 1/13). All successfully transformed tumor cell cultures showed a relatively stable karyotype in the pre‐crisis stage and a high mitotic index, were T‐antigen positive, and had an extended life span in vitro.
Distinct breakpoints in band 11q23 of the t(4;11) and t(11;14) associated with leukocyte malignancy
Authors: Radice Paolo , Tunnacliffe Alan
Published: February 2007

Several non‐random translocation breakpoints associated with leukemia or lymphoma have been shown to occur in chromosome band 11q23 between the genes CD3G and PBGD, a distance of approximately 750 kb. A combination of yeast artificial chromosome (YAC) cloning, in situ hybridization, and pulsed field gel electrophoresis (PFGE) experiments has further refined the interval containing one of these breakpoints, lies in a region of approximately 100 kb, situated 100 kb distal to CD3G. Furthermore, we show that a second 11q23 breakpoint, t(11;14)(q23;q32), which was also previously mapped between CD3G and PBGD, is distinct from that of the t(4;11) chromosome. The 11q23 sequences that are involved at the t(11;14) breakpoint are not present in a YAC containing the t(4;11) breakpoint. The t(11;14) breakpoint has been localized on the PFGE map of the CD3G‐PBGD interval and is at least 110 kb distal to the t(4;11) breakpoint, thus demonstrating heterogeneity among 11q23 breakpoints.
Quantitative acute leukemia cytogenetics
Authors: Mitelman Felix , Heim Sverre
Published: February 2007

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,551 cases of acute lymphocytic leukemia (ALL), we have attempted to quantify the information value of finding the typical ALL‐ and AML‐associated chromosome aberrations. Sensitivity, specificity, and predictive value of finding or not finding a given aberration were calculated for several diagnostic scenarios: for the differential diagnosis between ALL and AML when the patient is known to have acute leukemia, for the differential diagnosis among AML FAB subtypes in a patient with known AML, and for the differential diagnosis between ALL FAB subtypes in a patient with known ALL. The specificities were generally high, close to I. The highest sensitivities in AML were found for +8, t(15;17)(q22;q11), t(8;21)(q22;q22), and‐7 (all > 0.1), and in ALL for t(9;22)(q34;q11), t(4;11)(q21;q23), and +21 (again all >0.1). In the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for t(9;11)(p21;q23) in M5. In the ALL subtypes, the highest sensitivities were 0.71 and 0.11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for t(9;22)(q34;q11) in L2, and 0.18 and 0.13 for +21 and t(4;11)(q21;q23), respectively, in LI. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26), t(6;9)(p23;q34), t(7;11)(p15;p15), t(8;16)(p11;p13), t(8;21)(q22;q22), t(15;17)(q22;q11), and, as sole anomalies, for +4, +9, and + 11. In the reverse comparison, ALL versus AML, positive predictive values of 1.0 were found for t(1;14)(p32–34;q11), dup(1)(q12–21q31–32), t(2;8)(p12;q24), t(8;14)(q24;q32), t/dic(9;12)(p11–12;p11–13), t(10;14)(q24;q11), and t(11;14)(p13;q11). Among the AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91 for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16), and 0.82 for M5 if t(9;11). Among the ALL subtypes, positive predictive values of >0.8 were reached only for the L3‐associated aberrations t(2;8) (1.0), t(8;14)(0.95), t(8;22)(0.87), and dup(1) (0.80). The highest negative predictive values were in AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96 that the patient does not have L3 if a t(8;14) is not detected.
Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism
Authors: Jones Michael H. , Nakamura Yusuke
Published: February 2007

Loss of heterozygosity at the TP53 locus occurs frequently in many types of cancer and requires polymorphic markers for detection. Several polymorphisms at the TP53 locus have been described previously, and polymerase chain reaction (PCR)‐based assays have been developed to detect these polymorphisms. However, these polymorphisms have relatively low levels of heterozygosity and are often uninformative. We report here the detection of loss of heterozygosity at the TP53 locus in various human cancers by using a highly informative dinucleotide repeat polymorphism.
No alterations in exon 21 of the RBI gene in sarcomas and carcinomas of the breast, colon, and lung
Authors: Hovig Eivind , Smith‐Sørensen Birgitte , Gebhardt Mark C. , Ryberg David , Lothe Ragnhild , Børresen Anne‐Lise
Published: February 2007

Studies of mutant genotypes of the retinoblastoma susceptibility gene (RBI) in different solid tumors have mainly been concentrated on the demonstration of loss of heterozygosity (LOH) at both internal and external polymorphic sites. One reason for this is the complex organization of the gene. The p105RB protein has been shown to interact with both DNA and regulatory cellular proteins and oncoproteins. The amino acids encoded by exon 21 are implicated in several of these interactions. Both point mutations and intragenic deletions involving exon 21 have previously been reported in human tumors. We have examined RBI exon 21 from a number of human tumor types where significant LOH in or around the RBI gene has been reported. DNA from 78 primary tumors was amplified using the polymerase chain reaction (PCR) with primers covering exon 21, followed by constant denaturant gel electrophoresis (CDGE). The 78 tumors included 11 breast carcinomas, 30 nonsmall cell lung carcinomas, 6 colon carcinomas, and 31 sarcomas. The small cell lung cancer cell line NCI‐H209, previously shown to harbour a point mutation in codon 706: TGT‐ > TTT (Cys‐ > Phe), was detected using CDGE. Apart from this control mutant cell line, we did not detect any mutations in the examined region in any of the tumors.
Molecular analysis of a partial deletion of 22q in a central nervous system rhabdoid tumor
Authors: Biegel Jaclyn A. , Burk Carol D. , Parmiter Annette H. , Emanuel Beverly S.
Published: February 2007

We previously reported the non‐random occurrence of monosomy 22 in rhabdoid or atypical teratoid tumors of the brain in three young children. We now present cytogenetic and molecular studies of an additional rhabdoid tumor with the karyotype 46.XX, ‐ 9,‐22, + i( 1q), + der(22)t(9;22)(p 13;q11)/45,XX, ‐ 9,‐10,‐22, + i(1q), + der(22)t(9;22)(p 13;q11). These studies further demonstrate the involvement of chromosome 22, and they begin to define the critical region containing a gene or genes involved in the development or progression of rhabdoid tumors of the brain.
Detection of RAS mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization
Authors: Moul Judd W. , Theune Sheila M. , Chang Esther H.
Published: February 2007

Preliminary studies of RAS mutational activation in human testicular germ cell neoplasms have yielded conflicting results. Whereas two studies of clinical material revealed a significant incidence of N‐ and KRAS mutations, two studies of a variety of germ cell lines failed to document RAS mutations. To clarify the incidence of RAS mutations in these tumors, we studied archival paraffin‐embedded, formalin‐fixed orchiectomy specimens from 25 nonseminomas (NSGCT), 18 seminomas (SEM), and one Leydig cell tumor. For 14 of the 44 neoplasms, DNA was also available from nonmalignant testis adjacent to the tumor. Six age‐matched patients had testes removed because of nonmalignant disease and were studied as controls. Polymerase chain reaction (PCR) amplified the K‐, N‐, and HRAS 12, 13, and 61 codons of these specimens, and mutations were detected with mutation‐specific oligonucleotide probe hybridization of Southern and slot blots. Four mutations were found in KRAS 12 (4/44,[9.1 %]). One seminoma [1/18(5.6%)] contained the mutation GGT(GLY) → CGT(ARG), and three NSGCT [3/25(12%)] were found to have GGT(GLY) → GAT(ASP) mutations. One of the NSGCT mutations was detected in adjacent nonmalignant tissue, but the corresponding tumor did not contain any detectable mutation. No mutations were detected at KRAS 13 or 61, in NRAS or HRAS 12, 13, or 61, or in the control normal testes. PCR, slot blots, and hybridizations were performed twice by two separate investigators for confirmation of results. PCR‐generated mutation‐specific positive controls were created for all possible RAS mutations, and these along with wild‐type DNA controls were integral to interpretation of the oligonucleotide mismatch hybridization assay. By using positive and negative controls, we have detected a relatively low incidence of RAS mutations in archival human testicular germ cell tumors.
Identification of a whole‐arm translocation by in situ hybridization with directly fluorochrome‐labeled probes in a myelodysplastic syndrome
Authors: Bajalica Svetlana , Brøindum‐Nielsen Karen , Sørensen Anne‐Grethe , Pedersen Niels Tinggaård , Heim Sverre
Published: February 2007

A case of myelodysplasia was found to have a complex bone marrow karyotype, involving an apparent whole‐arm translocation between 17q and 18q. The application of a simplified fluorescence in situ hybridization technique, using directly fluorochrome‐labeled centromere‐specific alpha‐satellite DNA probes, demonstrated the presence of sequences from both chromosomes 17 and 18 in the centromere of the derivative chromosome. This proves that a true whole‐arm translocation had occurred. The case exemplifies how in situ hybridization analysis can be used to resolve interpretation problems in cancer cytogenetics.
Clinical impact of chromosome I aberrations in neuroblastoma: A metaphase and interphase cytogenetic study
Authors: Christiansen Holger , Schestag Joachim , Christiansen Nina M. , Grzeschik Karl‐Heinz , Lampert Fritz
Published: February 2007

Neuroblastoma tumors are characterized by aberrations of chromosome I. Rapid detection of these chromosomal aberrations at diagnosis could give important clues to outcome and therapy. We attempted to detect numerical and structural aberrations of chromosome I not only by classical metaphase cytogenetics but also by interphase cytogenetics in order to overcome difficulties of karyotyping due to diminished metaphase quality and quantity in primary neuroblastoma samples. Karyotypic changes of chromosome I in 53 primary neuroblastomas were evaluated. In addition, we successfully performed interphase cytogenetics using single and double in situ hybridization procedures with chromosome I ‐specific repetitive DNA probes on nuclei preparations obtained from 46 and 20 tumors, respectively. Polysomies of structurally normal chromosomes I were predominantly seen in tumors with good prognosis, whereas deletions of 1p material were nearly exclusively confined to progressive tumors. Numerical and structural chromosome I aberrations as studied by metaphase and interphase cytogenetics are thus valuable prognostic markers in neuroblastoma.
Isochromosome 1q in acute monocytic leukemia: A new nonrandom association
Authors: Hawkins Jacqueline M. , Wood Marion , Wright Faith , Seeker‐Walker Lorna M.
Published: February 2007

We report a case of de novo acute monocytic leukemia in a 25‐year‐old man in whom the sole clonal cytogenetic abnormality was an additional isochromosome Iq. Cytogenetic polymorphisms indicate that, in addition to the formation of the isochromosome, a duplication of the remaining normal chromosome I had taken place. Other reported cases suggest an association between acute monocytic leukemia and i(lq).
Cytogenetic studies on 19 papillary thyroid carcinomas
Authors: Antonini Patrick , Venuat Anne‐Marie , Caillou Bernard , Berger Roland , Schlumberger Martin , Bernheim Alain , Parmentier Claude
Published: February 2007

Short‐term cultures from 19 papillary thyroid adenocarcinomas revealed clonal numerical and/or structural chromosomal changes in 13 tumors, nonclonal abnormalities in one tumor, and only normal karyotypes in five tumors. Clonal abnormalities of chromosome 10 were present in three tumors, two of which had the translocation t(7; 10)(q35;q21). Numerical abnormalities of chromosome 17 were detected in two tumors.
Variant translocations in two Burkitt's lymphoma cell lines are located in the MLV14 locus
Authors: Galiego Marta I. , Lazo Pedro A.
Published: February 2007

The human MLV14 locus, located 20 kilobases 3′ of MYC, is rearranged in two Burkitt's lymphoma cell lines with either a t(2;8)(p 12;q24) or t(8;22)(q24;q 11). Alterations of MLV14 may have prognostic significance in some types of B‐cell malignancies.
Cytogenetic studies in subgroups of rhabdomyosarcoma
Authors: Whang‐Peng J. , Knutsen T. , Theil K. , Horowitz M. E. , Triche T.
Published: February 2007

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS‐E), alveolar (RMS‐A), and primitive (RMS‐P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS‐A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2; 13) was not present, but translocation of 13q to both I q and 2p was observed, der(l)t(l;l3)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodipl‐oid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t( 11;22)(q24;q 12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature. Published 1992 by Wiley‐Liss, Inc.
Characterization of a complex chromosomal rearrangement maps the locus for In vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q 13
Authors: Flejter Wendy L. , McDaniel Lisa D. , Askari Minoo , Friedberg Errol C. , Schultz Roger A.
Published: February 2007

Microcell‐mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP‐D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261–265, 1992). Additionally, those studies demonstrated a role for the excision repair cross‐complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP‐D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q‐arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2‐q13.3, a result consistent with the notion that the in vitro correction of XP‐D cells by the Tneo chromosome is rendered by die ERCC2 locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex rearrangements.
Two diverged human homeobox genes involved in the differentiation of human hematopoietic progenitors map to chromosome I, bands q41–42.I
Authors: Najfeld Vesna , Menninger Joan , Ballard Stephen Gwyn , Deguchi Yasuhiro , Ward David C. , Kehrl John Howard
Published: February 2007

Proteins encoded by homeobox containing genes are sequence‐specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes, HB9 and HB24, are highly expressed in CD34‐positive marrow cells but not in CD34‐depleted marrow cells, Their expression is readily down‐regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated with HB9 (3 kb) and HB24 (6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. Both HB9 and HB24 DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R‐like banding) and by DAPI staining (G‐like). The results demonstrate that the loci of the HB24 and HB9 genes are within bands 1q41–q42.1. A cohybridization experiment utilizing both probes with two‐color fluorescence imaging could not resolve separate loci for the two genes. © 1992 Wiley‐Liss, Inc.
Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas
Authors: Ransom David T. , Ritland Steve R. , Kimmel David W. , Moertel Cheryl A. , Dahl Richard J. , Scheithauer Bernd W. , Kelly Patrick J. , Jenkins Robert B.
Published: February 2007

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. © 1992 Wiley‐Liss, Inc.
Clonal cytogenetic abnormalities and telomeric associations in a fibroxanthoma of the stomach
Authors: Seruca Raquel , Carneiro Fátima , Soares Paula , Fonseca Elsa , Castedo Sérgio
Published: February 2007

A cytogenetic study of a fibroxanthoma (fibrous histiocytoma) of the stomach revealed a clonal structural abnormality involving chromosome 12 and frequent telomeric associations between the short arm of chromosome 12 and different chromosomes. A marker chromosome possibly derived from chromosome 11 was also present. This is the second reported case of gastric fibroxanthoma and the first studied cytogenetically. © 1992 Wiley‐Liss, Inc.
Identification of a tumor marker chromosome by flow sorting, DNA amplification in vitro, and in situ hybridization of the amplified product
Authors: Boschman Gert A. , Buys Charles H. C. M. , Van Der Veen Anneke Y. , Rens Wim , Osinga Jan , Slater Rosalyn M. , Aten Jacob A.
Published: February 2007

A method combining flow sorting and molecular cytogenetic techniques for the identification of unknown marker chromosomes is described. In this study, the bladder tumor cell line J82 was used, which was known to carry a marker chromosome of the size of chromosome 7 in every cell. From the cytogenetic analysis of Q‐banded metaphase cells, it was shown to be composed of ∼40% presumably the greater part of chromosome 20 and for the rest microscopically unidentifiable material. This marker chromosome was found using flow cytometric analysis to form an independent peak and hence was suitable for isolation using dual‐parameter sorting after staining with Hoechst 33258 and chromomycin A3. Subsequently, the marker was isolated by dual‐parameter sorting. DNA amplification of 300 isolated chromosomes by polymerase chain reaction (PCR) using the Alu‐primer Bk33 and the LINES‐primer LH5 was carried out. After purification of the amplified product, a yield of 5 μm of DNA was obtained. The DNA was labelled using Bio‐11‐dUTP and applied to human lymphocyte metaphase cells in a suppressive in situ hybridization procedure. Fluorescence was visible over chromosome 20 and over the distal one‐half of 6p. Together the fluorescent regions accounted for only ∼60% of the marker length, indicating a possible duplication of chromosome 20 material. This was confirmed by applying bicolor in situ hybridization using chromosome 6‐ and 20‐specific DNA libraries to metaphase cells of the J82 cells. © 1993 Wiley‐Liss, Inc.
Cytogenetic demonstration of gene amplification in a primary intracranial germ cell tumor
Authors: Albrecht Steffen , Armstrong Dawna L. , Mahoney Donald H. , Cheek William R. , Cooley Linda D.
Published: February 2007

We report the cytogenetic analysis of a primary pineal germinoma. The modal chromosome number was 81. Multiple numerical and structural chromosome abnormalities were noted along with a large homogeneously staining region (HSR). No isochromosome 12p was identified. © 1993 Wiley‐Liss, Inc.