bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the ERBB2 protein in benign and malignant salivary gland tumors
Authors: Stenman Goran , Sandros Jens , Nordkvist Anders , Mark Joachim , Sahlin Pelle
Published: February 2007

Fifty‐two primary human salivary gland tumors were analyzed for expression of the p 185ERBB2 protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25–100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow‐up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate that ERBB2 activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland tumors.
Clonal cytogenetic abnormalities in Hodgkin's disease
Authors: Ladanyi Marc , Parsa Nasser Z. , Offit Kenneth , Wachtel Mitchell S. , Filippa Daniel A. , Jhanwar Suresh C.
Published: February 2007

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non‐Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent Cytogenetic picture of HD. Over a 6 1/2‐year period, we received 95 specimens of HD for Cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81 %) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte‐depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near‐tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q 13), del(6)(q23), i(6p)). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1 p, 1 q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki‐1 ‐positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a Cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.
Mutation in the TP53 gene in colorectal carcinoma detected by polymerase chain reaction
Authors: Han Eun‐Soo , Moyer Mary Pat , Naylor Susan , Sakaguchi Alan Y.
Published: February 2007

The human TP53 gene is a possible tumor suppressor since TP53 gene mutations are observed in >70% of sporadic colorectal carcinoma DNAs. In genomic DNAs from seven colon cancer cell samples, a 405 base pair DNA fragment containing exon 5, intron 5, and exon 6 of the TP53 gene was amplified by polymerase chain reaction and analyzed for mutations. One sample [human colon cancer (HCC) 278] was found to have a TP53 mutation altering the amino acid glutamine 167 in exon 5. A deletion of 2 bases changed glutamine 167 (CAG) to alanine (GCA) and the resulting frame‐shift produced an in‐frame stop codon at amino acid 179. While the normal TP53 gene gives rise to a 53 kD protein, the estimated size of this mutant TP53 protein if expressed would be approximately 20 kD.
Allelic 3p Deletions in High‐Grade Carcinomas After Transformation In Vitro of Human Uroepithelial Cells
Authors: Klingelhutz Aloysius J. , Wu Shi‐Qi , Bookland Elizabeth A. , Reznikoff Catherine A.
Published: February 2007

Restriction fragment length polymorphism (RFLP) analysis for allelic losses on the chromosome arm 3p were performed on independent carcinomas produced in athymic nude mice after transformation in vitro of a pseudodiploid clonal SV40‐immortalized human uroepithelial cell line (SV‐HUC). We analyzed ten primary carcinomas with heterogeneous phenotypes for deletions on 3p by using three informative probes, D3S30, D3S2, and D3F15S2, which map to the 3p11‐p14, 3p21.1, and 3p21 regions, respectively. Five of the ten primary cancers showed reduction to homozygosity with at least one of the probes, and all five cancers were high‐grade and poorly differentiated. We also analyzed six carcinomas that arose after progression of low‐grade cancers, either spontaneously or after exposure to a human bladder carcinogen, to higher grades (progressed carcinomas). Four of the six exhibited 3p allelic loss. No preferential loss of a specific 3p allele was observed in any of the carcinomas. In addition, whereas most of the carcinomas showed allelic loss for all three of the probes, indicating a large‐scale deletion, several of the carcinomas exhibited losses for only one or two of the probes, thus making it possible, along with the cytogenetic data, to define the least common region of deletion to 3p13→p14.2. These results support the hypothesis that nonrandom loss of a gene or genes on 3p leads to the development of cancer. Furthermore, these findings associate deletion of a putative 3p13→p14.2 tumor suppressor gene region with the development of high‐grade uroepithelial carcinomas.
Characterization of Marker Chromosomes in Namalva Cells by Chromosomal In Situ Suppression (CISS) Hybridization and R‐Banding
Authors: Ruppersberger Peter , Arnold Michaela , Zankl Heinrich , Scherthan Harry
Published: February 2007

Chromosomal in situ suppression (CISS) hybridization was used to investigate the distribution of material of chromosomes 1 and 5 present in marker chromosomes of Namalva cells. The Namalva cell line, established from a Burkitt's lymphoma, exhibits a highly variable female karyotype with a large number of marker chromosomes. Libraries from sorted human chromosomes 1 and 5 were used to delineate material of these chromosomes present in the Namalva karyotype. We used the DAB/peroxidase reaction and reflection contrast microscopy for detection of biotinylated hybrid molecules. Identification of chromosomes was achieved by fluorescent R‐banding after CISS hybridization, which allowed the assignment of hybridized regions to the particular marker chromosomes. After CISS hybridization with a chromosome I library, the normal chromosome I was labelled as well as a large marker MI and the long arm of marker M3. Using a chromosome 5 library it could be shown that the distal part of the long arm of one chromosome 5 was translocated to marker M2. The normal chromosome 5 was completely labelled. The present investigation demonstrates the advantage of combining CISS hybridization and banding for the identification of complex, rearranged tumor karyotypes.
Gene Amplification and Gene Dosage in Cell Lines Derived From Squamous Cell Carcinoma of the Head and Neck
Authors: Yin Xiao‐Ying , Donovan‐Peluso Maryann , Whiteside Theresa L. , Johnson Jonas T. , Day Roger , Herberman Ronald B. , Locker Joseph
Published: February 2007

Gene amplification and related alterations in gene dosage were analyzed in a series of 34 cell lines derived from different human head and neck squamous cell carcinomas (SCCHN). INT2 gene amplification was observed in 62%, MYC gene amplification in 24%, and EGFR gene amplification in 21 % of the cell lines. There was a strong correlation between EGFR gene amplification and increased copies of the ERBB2 gene on chromosome 17, suggesting a synergistic selection for these two genes either during cancer progression or in culture. Two abnormalities showed a significant correlation with clinical course: MYC gene amplification showed an inverse correlation with tumor recurrence (r = ‐ 0.44, p = 0.01), and a small increase in MYCL gene copies on chromosome I correlated with the presence of metastases (r = 0.61, p = 0.001). This altered MYCL gene dosage might represent a chromosome translocation rather than true gene amplification. In addition to gene amplification, 79% of the cell lines had increased copies of chromosome 8. Comparison of the cell lines with several of the corresponding primary tumors demonstrated that most gene amplifications were already present in the primary tumors, although some appeared de novo in cell culture. These studies indicate that gene amplification, especially of INT2, is a prominent abnormality in head and neck squamous cell cancer. Aneuploidy and chromosomal lesions other than gene amplification were also found to alter the dosage of several oncogenes specifically.
TP53 tumor suppressor gene: A model for investigating human mutagenesis
Authors: Fromentel Claude Caron De , Soussi Thierry
Published: February 2007

More than 350 independent point mutations of the TP53 gene, found in a wide variety of human cancers, were compiled and analysed. From this study, we confirm the presence of four hot‐spot regions which colocalize with some highly conserved domains of the protein. We also define a new hot‐spot region which is observed predominantly in lung tumors. Analysis of the mutational events suggests the direct involvement of environmental carcinogens in lung tumors and hepatocarcinomas, and spontaneous mutagenesis generating essentially CpG transitions in most of the remaining ones. Furthermore, we demonstrate in this work that the TP53 gene is an informative model with which to study the molecular mechanisms of mutagenesis in the human genome.
Cytogenetic analysis of 57 primary prostatic adenocarcinomas
Authors: Lundgren Rolf , Mandahl Nils , Heim Sverre , Mitelman Felix , Henrikson Hans , Limon Janusz
Published: February 2007

Cytogenetic analysis after short‐term culture in vitro of primary tumor samples was attempted in 82 patients with prostatic cancer. Tumor material was obtained by radical prostatectomy or transurethral resection. Successful cytogenetic studies were performed on 57 tumors of which five were well, 30 moderately, and 22 poorly differentiated adenocarcinomas. Only normal karyotypes were found in 24 tumors. Structural nonclonal aberrations were detected in 18 and clonal karyotypic abnormalities in 15 tumors. The most common clonal numerical aberration was loss of the Y chromosome; a missing Y was found in six tumors, in three of these as the sole anomaly. Clonal structural chromosomal rearrangements, usually accompanied by numerical changes, were detected in 12 tumors. The rearrangements involved 18 of the 22 autosomes and the X chromosome. Chromosomes 1, 7, and 10 were most frequently affected. Deletions, duplications, inversions, insertions, and balanced as well as unbalanced translocations were represented. The breakpoints in chromosome 1 were scattered along both the short and long arms with no obvious clustering, whereas those in chromosomes 7 and 10 were clustered at bands 7q22 (two deletions and two duplications in four different tumors) and 10q24 (two translocations, one deletion, and one inversion in four tumors). One additional tumor displayed a derivative chromosome 10 with a breakpoint in 10q23, and one had monosomy 10. Altogether, these abnormalities resulted in loss of 10q24→qter in five tumors. Monosomy 8 and rearrangements of the short arm of chromosome 8 leading to loss of 8p21→pter were seen in four tumors. Double minute chromosomes were found in two tumors.
Chromosome aberrations in 35 primary ovarian carcinomas
Authors: Pejovic Tanja , Heim Sverre , Mitelman Felix , Mandahl Nils , Flodérus Ulla‐Maria , Furgyik Stefan , Willén Helena , Baldetorp Bo , Himmelmann Anna , Elmfors Bengt , Helm Göran
Published: February 2007

Cytogenetic analysis was performed on short‐term cultures of primary ovarian carcinomas from 62 patients. Cytogenetic analysis was successful in 59 cases. Clonal chromosome aberrations were detected in 35 tumors. Only numerical changes or a single structural change were found in five carcinomas: trisomy 12 was the sole anomaly in two tumors, one tumor had the karyotype 50,XX, + 5, + 7, + 12, + 14, a fourth tumor had a balanced t(l;5), and the fifth tumor had an unbalanced t(8; 15). The fact that four of these five carcinomas were well differentiated suggests that simple karyotypic changes are generally characteristic of these less aggressive ovarian tumors. The majority of the cytogenetically abnormal tumors (n = 30) had complex karyotypes, with both numerical and structural aberrations and often hypodiploid or near‐triploid stemlines. The numerical imbalances (comparison with the nearest euploid number) were mostly losses, in order of decreasing frequency – 17, – 22, – 13, –8, – X, and – 14. The structural aberrations were mostly deletions and unbalanced translocations. Recurrent loss of genetic material affected chromosome arms 1p, 3p, 6q, and 11p. The breakpoints of the clonal structural abnormalities clustered to several chromosome bands and segments: 19p13, 11p13–15, 1q21–23, 1p36, 19q13, 3p12–13, and 6q21–23. The most consistent change (16 tumors) was a 19p + marker, and in 12 of the tumors the 19p + markers looked alike.
Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas
Authors: Andersen Tone I. , Gaustad Astrid , Børresen Anne‐Lise , Farrants George W. , Nesland Jahn M. , Ottestad Lars , Tveit Kjell M.
Published: February 2007

Fifty‐nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor‐negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor‐negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.
Reciprocal translocation t(12;22)(q13;q13) in clearcell sarcoma of tendons and aponeuroses
Authors: Stenman Göran , Kindblom Larsgunnar , Angervall Lennart
Published: February 2007

Clearcell sarcoma is a rare soft tissue sarcoma that displays certain similarities to malignant melanoma. In this paper we describe the karyotypic findings and in vitro growth characteristics of a shorttermcultured clearcell sarcoma. The cultured tumor cells had preserved immunohistochemical characteristics and certain ultrastructural features of the primary tumor, including positivity for vimentin, S‐100 protein, and a melanomaassociated antigen, supporting the authenticity of the cultured cells. Cytogenetic analysis revealed an abnormal stemline karyotype of 49,XY, –1, + 8, + 8, + 12, + der(l)t(1;?)(p36.1 –.3;?), t(12,22)(q13;q13). A similar or identical t(12;22) was recently reported in two of four clear‐cell sarcomas. It is suggested that the t(12;22)(q13;q13) is a primary cytogenetic abnormality in clear‐cell sarcoma and distinguishes this tumor type from malignant melanoma.
Chromosomal abnormalities in skin following total body or total lymphoid irradiation
Authors: Rubin Charles M. , Nesbit Mark E. , Kersey John H. , Arthur Diane C. , Kim Tae H.
Published: February 2007

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G‐banded chromosome analysis. Four biopsies were from three patients who had high‐dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high‐dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49–88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.
Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma: Correlation between southern blot and cytogenetic analyses
Authors: Tiainen Marianne , Kere Juha , Knuutila Sakari , Tammilehto Lauri , Mattson Kann
Published: February 2007

Southern blot hybridization studies were performed on 23 mesothelioma primary tumor specimens to detect chromosome 1‐, 7‐, and 22‐specific numerical changes, gene amplifications, and gene rearrangements. The molecular findings were compared with previous cytogenetic findings. No gene rearrangements or amplifications were detected. A numerical abnormality of chromosome 7 was detected by Southern blot analysis in two cases in which no numerical abnormality had been detected by the previous chromosome study. A numerical aberration of chromosome 22 was detected in five cases, which was compatible with the cytogenetic finding of monosomy 22 in these cases. The Southern blot results for the copy numbers of chromosomes 7 and 22 were concordant with the cytogenetic findings in 65%–80% of the cases.
Molecular cytogenetic analysis of a complex t(10;22;11) translocation in ewing's sarcoma
Authors: Speleman Frank , Roy Nadine Van , Leroy Jules G. , Dierick Anne Marie , Uyttendaele Dirk , Wiegant Joop
Published: February 2007

Fluorescence in situ hybridization (FISH) using chromosome‐specific plasmid libraries and chromosome region‐specific DNA markers allowed the characterization of a t(10;22;11) (p11.2;q12;q24) in a Ewing's sarcoma (ES). This study illustrates the usefulness of molecular cytogenetic analysis of ES, especially for determining the localization of the translocated 11q24–25 segment in complex or variant translocations.
Different localization of epstein‐barr virus genome in two subclones of the burkitt lymphoma cell line namalwa
Authors: Gargano Silvia , Caporossi Daniela , Gualandi Giampiero , Calef Enrico
Published: February 2007

The Epstein‐Barr virus genome contained in the Burkitt lymphoma line Namalwa was previously localized to the short arm of chromosome I. Analysis of a different subline of the same Namalwa line by means of Southern analysis carried out on genomic DNA, as well as in situ hybridization, showed a localization on the X chromosome.
Loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal melanoma
Authors: Horsthemke Barnhard , Prescher Gabriele , Becher Reinhard , Bornfeld Norbert
Published: February 2007

Uveal melanoma is the most frequent primary intraocular tumor. The etiology is unknown. Using neutral DNA polymorphisms on chromosomes 2, 3, and 8, we have detected loss of chromosome 3 alleles in 8 of 13 tumors and multiplication of chromosome 8 alleles in 6 of 11 tumors. No anomalies at a locus on chromosome 2 were found in 10 of 10 tumors. These results confirm and extend previous cytogenetic findings and suggest that a tumor suppressor gene on chromosome 3 and an oncogene on chromosome 8 may be involved in the formation or progression of this tumor.
Cytogenetic analysis by chromosome painting using dop‐pcr amplified flow‐sorted chromosomes
Authors: Telenius HÅKan , Ponder Bruce A. J. , Tunnacliffe Alan , Pelmear Adèle H. , Carter Nigel P. , Ferguson‐Smith Malcolm A. , Behmel Annemarie , Nordenskjöld Magnus , Pfragner Roswitha
Published: February 2007

A novel polymerase chain reaction (PCR) technique has been combined with chromosome flow sorting to characterise two lymphoblastoid cell lines and one medullary thyroid carcinoma cell line carrying translocations close to the locus for multiple endocrine neoplasia type 2A (MEN 2A). Five hundred copies of the derivative chromosome(s) were flow sorted from each cell line and amplified by degenerate oligonucleotide‐primed–polymerase chain reaction (DOP‐PCR). This generated pools of DNA sequences corresponding to the abnormal chromosomes, which were then used as probes in fluorescence in situ hybridisation (FISH) experiments on normal metaphase cells. The resultant chromosome paints revealed the portions of the normal chromosomes related to those involved in the translocations. By this technique, translocation breakpoints in bands p15, q11.2, and q21 of chromosome 10 were defined in the above cell lines, in two cases refining previous cytogenetic data. This study shows that flow sorting of aberrant chromosomes and chromosome painting can be used as a rapid aid to cytogenetic analysis, particularly in cases of difficult karyotypes, such as tumours. Furthermore, the DOP‐PCR technique described here will have applications to other areas of genome analysis, such as cloning of new markers; its design will allow a general and representative amplification to occur from any starting DNA in any species.
Low chromosome number in chromophobe renal cell carcinomas
Authors: Kovacs Angela , Kovacs Gyula
Published: February 2007

Cytogenetic analysis revealed low chromosome number, telomeric association, and pulverisation of chromosomes in three chromophobe renal cell carcinomas. One fully karyotyped and a previously published case showed the common loss of chromosomes 1, 2, 6, 10, 13, 17, and 21.
Detection of amplified dna sequences in human tumor cell lines by fluorescence in situ hybridization
Authors: Bar‐Am Irit , Mor Orna , Shiloh Yosef , Avivi Lydia , Yeger Herman
Published: February 2007

An unambiguous and rapid characterization of amplified DNA sequences in tumor cells is important for the understanding of neoplastic progression. This study was conducted to evaluate the potential of fluorescence in situ hybridization (FISH) to identify such amplified DNA sequences in human tumor cell lines. Applying this technique, we followed the metaphase location and interphase position of amplified DNA sequences corresponding to the SAMK, MYC, and MYCN genes in four cell lines derived from human tumors: two gastric carcinoma lines (KATO III and SNU‐16), a neuroblastoma (NUB‐7), and a neuroepithelioma (NUB‐20) line. In metaphase cells of KATO III, NUB‐7, and NUB‐20 lines, the amplified regions were clearly visible and easily identified at an intrachromosomal location: in KATO III and NUB‐7 at a terminal position and in NUB‐20 at an interstitial position. In SNU‐16, on the other hand, the amplified SAMK and MYC sequences were identified in extrachromosomal double minute chromosomes (DMs). In this line, the SAMK and MYC sequences were coamplified in the same cells and were colocated on the same DMs. FISH also allowed the identification of amplified DNA sequences in nondividing cells, enabling us to distinguish, at interphase, whether the amplification gave rise to intrachromosomal amplified regions (IARs) or to extrachromosomal DMs. The FISH technique also allowed us to determine at metaphase as well as at interphase the extent of amplification and the size of the IARs.
Rearrangements of chromosome arm 3q in poorly differentiated nasopharyngeal carcinoma
Authors: Waghray Manjula , Parhar Ranjit S. , Al‐Sedairy Sultan , Taibah Khalid
Published: February 2007

Cell lines were established from fresh tumor biopsies from two Saudi patients with poorly differentiated nasopharyngeal carcinoma (NPC). Cytogenetic analysis on Giemsa‐banded metaphase cells revealed complex, abnormal karyotypes in both patients with modal chromosome numbers of 77 and 52. A der(3)dup(3)(q25‐q2?7) or t(3;?)(q27;?) was observed in both cell lines. The rearrangements involving chromosomes X, 1, 4, 6, 7, 8, 12, 13, 15, 17, and 22 in the first patient and 1, 6, and 22 in the second patient could represent clonal evolution.
Translocation t(5;19): A recurrent change in thyroid follicular adenoma
Authors: Roque Lúcia , Clode Ana , Soares Jorge , Castedo Sérgio
Published: February 2007

The cytogenetic study of a follicular thyroid adenoma revealed a t(5;19)(q13;q13.3). This is the second report of a translocation between chromosomes 5 and 19 in a thyroid follicular adenoma.
Characterization of the submicroscopic deletion in the small‐cell lung carcinoma (SCLC) cell line U2020
Authors: Drabkin Harry A. , Mendez Mike J. , Rabbitts Pamela H. , Varkony Terry , Bergh Jonas , Schlessinger Joseph , Erickson Paul , Gemmill Robert M.
Published: February 2007

The small‐cell lung carcinoma cell line U2020 contains a submicroscopic, homozygous deletion that removes a chromosomal segment within 3p13‐p14, including the locus D3S3. We have sublocalized 49 additional probes to the 3p13‐p14.2 region and have identified 7 new DNA markers that arise from within the U2020 deletion. The estimated size of the deletion, based on marker density, is approximately 4–5 megabases (Mb). Including D3S3, 7 of the 8 markers have been linked by pulsed‐field gel (PFG) electrophoresis over an area of approximately 2 Mb. Including the one unlinked marker, PFG analysis accounts for about 3 Mb of the region. The U2020 deletion appears confined to the 3p13‐p14.2 region and does not include the candidate tumor suppressor gene, protein‐tyrosine phosphatase gamma (PTPG).
Viral integration and fragile sites in human papillomavirus‐lmmortalized human keratinocyte cell lines
Authors: Smith Patricia P. , Friedman Cynthia L. , Bryant Eileen M. , McDougall James K.
Published: February 2007

Human papillomavirus (HPV) types 16 and 18 integration sites were mapped in six HPV‐immortalized human keratinocyte cell lines by fluorescence in situ hybridization (FISH). Mapping of HPV sequences in these cell lines revealed that HPV integration varied in copy number and location but that integration sites were stable over extended passages in culture. Integration occurred at different sites throughout the genome and did not correspond to the location of specific cellular genes. However, integration sites were consistent with integration near or within known fragile sites in five of the six cell lines. Induction of aphidicolin‐sensitive fragile sites in one cell line prior to in situ hybridization revealed that integrated HPV DNA was disrupted by fragile‐site expression, suggesting that integration occurred within a fragile site.
Translocation t(11; 14)(q 13;q32) in chronic lymphoid disorders
Authors: Brito‐Babapulie V. , Ellis J. , Matutes E. , Oscier D. , Khokhar T. , MacLennan K. , Catovsky D.
Published: February 2007

The translocation t( 11; I4)(q 13;q32) has been described in a spectrum of B‐lymphoproliferative diseases and involves a putative oncogene, BCLI, which maps to chromosome band 11q13. Recent evidence indicates that this abnormality may delineate particular subtypes of lymphoma, such as intermediate lymphocytic and centrocytic lymphomas. Thus the possible significance of the t(111;14) within B‐cell disorders should be reexamined in the light of a more objective approach to classifying these diseases by morphology, histology, and immunophenotype. We describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with chronic lymphoid disorders in whom clonal chromosome abnormalities were detected. All the cases were leukemic: prolymphocytic (B‐PLL; 4/15 cases), chronic lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non‐Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and follicular (I case). None of the CLL (25) or hairy cell leukemia cases (15) had t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B cells with lymphoplasmacytic features as judged by morphology and immunophenotype.
Chromosome changes in a case of hibernoma
Authors: Dal Cin Paola , Van Damme Boudewijn , Hoogmartens Michel , Van Den Berghe Herman
Published: February 2007

Cytogenetic analysis of a rare adipose tissue tumor, hibernoma, a benign proliferation of the brown fat, is presented for the first time. A complex translocation involving bands 1p36, 2q33, 5q22, and 11q13 was found as the sole chromosome abnormality.
Non‐random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma
Authors: Sisley Karen , Cottam David W. , Rennie Ian G. , Parsons M. Andrew , Potter Anthony M. , Potter Christopher W. , Rees Robert C.
Published: February 2007

We present ten cases of posterior uveal melanoma which were karyotyped after short‐term culture. One tumour had a normal chromosome complement. The remaining nine tumours were cytogenetically abnormal, with chromosomes 3, 6, 8, 11, and 13 most frequently involved. Abnormalities of chromosome 13 were seen in two cases, chromosome 11 in three cases, and chromosomes 3, 6, and 8 in five cases. Four tumours, all derived from the ciliary body, demonstrated monosomy 3 and i(8q), confirming the involvement of these aberrations with a subgroup of uveal melanomas arising from the ciliary body.
Whole‐arm t(1;16) and i(1q) as sole anomalies identify gain of 1 q as a primary chromosomal abnormality in breast cancer
Authors: Pandis Nikos , Heim Sverre , Bardi Georgia , Idvall Ingrid , Mandahl Nils , Mitelman Felix
Published: February 2007

Cytogenetic analysis of four ductal breast carcinomas revealed net gain of 1 q in all tumors. In the first tumor, the only change was that one chromosome 16 was replaced by a derivative chromosome consisting of 16p and 1q. The same unbalanced whole‐arm translocation was also found in the second tumor, as the only aberration in one of four abnormal clones. In the last two cases, which also were characterized by cytogenetically unrelated clones, an extra i(1q) was present in one clone in both tumors as the sole aberration. Our findings suggest that gain of 1 q is a primary chromosomal abnormality in breast carcinomas, in the sense that it is an early event that precedes the acquisition of more complex changes.
Recurrent abnormalities of chromosome bands 10q23–25 in non‐Hodgkin's lymphoma
Authors: Speaks Susan L. , Sanger Warren G. , Masih Aneal S. , Harrington Douglas S. , Hess Michelle , Armitage James O.
Published: February 2007

Many nonrandom chromosome abnormalities have been associated with non‐Hodgkin's lymphomas (NHL). Some of these are nonspecific changes seen in many different histologic subtypes. We describe a series of abnormalities of chromosome bands 10q23–25 seen in 159 consecutive NHL patients with abnormal cytogenetic findings. The proportion of karyotypes with abnormalities of 10q varied from 3% among the immunoblastic lymphomas to 67% in the diffuse large cleaved cell lymphomas. Seventeen (10.7%) had abnormalities of 10q23–25. All but one of these were B‐cell tumors. The abnormalities consisted of six deletions and 11 translocations. Sixteen of the 17 patients had the 10q abnormality when cells were first karyotyped. The remaining patient acquired the 10q abnormality in the third of a series of biopsies. In the follicular histologic subtypes [follicular small cleaved cell (FSC), follicular mixed small cleaved and large cell (FM), and follicular large cell noncleaved (FL‐NC)], abnormalities of 10q were found in nine patients, all in association with abnormalities of 14q32. Seven of these were associated with the t(14;18)(q32;q21). Overall, 10q23–25 abnormalities were observed in 11.9% (8/67) of low‐grade [small lymphocytic (SL), FSC, and FM] lymphoma cases. DNA was available from five patients with abnormalities of 10q and was probed for rearrangements with the HOX11 (TCL3) oncogene probe. As expected, we did not find such rearrangements in these five patients with B‐cell tumors. Abnormalities of 10q23–25 have been reported previously in NHL but not at this frequency.
Molecular cloning and analysis of chromosome band 11q23 involved in leukaemia‐associated translocations
Authors: Das Soma , Kearney Lyndal , Bower Mark , Chaplin Tracy , Riley John H. , Anand Rakesh , Young Bryan D.
Published: February 2007

Three overlapping yeast artificial chromosomes (YACs) spanning a 780 kb region of DNA around the CD3 locus on chromosome 11 have been isolated and characterised. The individual cloned regions have been mapped by in situ hybridisation to chromosome band 11 q23, and a restriction enzyme map of this region has been constructed. The positions of these clones in relation to a series of leukaemia‐associated chromosomal translocations has also been determined. It was concluded that, although two clones lay entirely proximal to the breakpoints examined, the third clone (13HH4) encompassed the breakpoints for the translocations t(4;11), t(6;11), and t(9;11). The t(9;11) was observed in an acute myeloid leukaemia in a patient previously treated for an unrelated malignancy. It would thus appear that the breakpoints at chromosome band 11q23 occurring in therapy‐related leukaemias are in the same region as those found in adult and childhood acute leukaemias and may result from a common underlying mechanism.
Clonal 6p21 rearrangement is restricted to the mesenchymal component of an endometrial polyp
Authors: Fletcher Jonathan A. , Pinkus Jack L. , Lage Janice M. , Morton Cynthia C. , Pinkus Geraldine S.
Published: February 2007

Previous cytogenetic analyses revealed t(6;20)(p21;q 13) in two endometrial polyps. We karyotyped a large endometrial polyp in which 19 of 25 metaphase cells contained a t(1;6;4)(q21;p21;q 13). Subsequent combined immunohistochernical/cytogenetic analysis showed all aberrant metaphase cells to be of mesenchymal derivation, whereas epithelial cells from the polyp were diploid. These studies indicate that rearrangement of chromosome band 6p21 is a characteristic cytogenetic aberration in the stromal component of endometrial polyps.
Molecular analysis of a new translocation, t(X;I4)(q28;qII), in premalignancy and in leukaemia associated with ataxia telangiectasia
Authors: Thick J. , Sherrington P. D. , Fisch P. , Taylor A. M. R. , Rabbitts T. H.
Published: February 2007

The disease ataxia telangiectasia (A‐T) is a multifaceted disorder in which patients have an increased chance of developing a T‐cell leukaemia, often with abnormalities of chromosome 14, but sometimes with rare translocations, like t(X; 14)(q28;q11). We describe the cloning of the breakpoint of one such novel t(X;14) from an A‐T patient. The translocation breaks within the T cell receptor α chain gene on chromosome 14 at band q11 and in a region of the X chromosome, within about 1 Mb of the telomere of the long arm. The patient subsequently developed T‐cell prolymphocytic leukaemia (T‐PLL), and molecular examination showed that the tumour cells carried the same t(X; 14) breakpoint as that cloned from the premalignant cells. The same breakpoint could be detected in blood samples taken as much as 5 years prior to diagnosis of T‐PLL. This suggests a role for the abnormality in the tumour development in this patient but implies that other mutational events were necessary for overt disease to become manifest. © 1992 Wiley‐Liss, Inc.
Recurring chromosome abnormalities in Hodgkin's disease
Authors: Döhner Hartmut , Bloomfield Clara D. , Frizzera Glauco , Frestedt Joy , Arthur Diane C.
Published: February 2007

Cytogenetic analysis was performed on lymph nodes or other tumor masses from 33 patients with Hodgkin's disease. Metaphase cells were obtained in 25 of the 33 cases. Analyzable abnormal clones were found in nine cases. Characteristic abnormalities included polyploidy and complex structural rearrangements nonrandomly involving certain chromosomal regions. Chromosomes most commonly gained were 2, 9, 11, 19, and 20, and those most often lost were 10, 13, 15, 16, 21, and Y. Translocation breakpoints clustered in bands 1p11–1p13, 1p36, 4q35, 14q11, and 15p11. In five patients, breakpoints were in bands to which T‐cell receptor genes have been mapped. No specific, recurring translocation was identified. There was, however, recurring loss of chromosomal material from 1q, 4q, 6q, and 17p. Loss or deletions of chromosomes 4 and 6 were found in five and six patients, respectively. Deletions overlapped; the smallest overlapping segments included bands 4q25–4q27 and 6q21 ‐6q23. The data suggest that loss of specific chromosomal regions may be important in the pathogenesis of Hodgkin's disease. With respect to tumor specificity, deletions of 4q are of particular interest because these have not been previously reported to occur nonrandomly in other human malignancies. © 1992 Wiley‐Liss, Inc.
Loss of heterozygosity on the long arm of chromosome 22 in pheochromocytoma
Authors: Tanaka Norifumi , Nishisho Isamu , Yamamoto Masayuki , Miya Akihiro , Shin Eisei , Karakawa Katsu , Fujita Shoichi , Kobayashi Tetsuro , Rouleau Guy A. , Mori Takesada , Takai Shin‐Ichiro
Published: February 2007

To identify the putative common deleted region on the long arm of chromosome 22 in pheochromocytoma, restriction fragment length polymorphism analysis was performed in 17 pheochromocytomas. All cases were heterozygous for at least one of the eight marker loci on 22q. Loss of heterozygosity (LOH) was observed in nine pheochromocytomas, of which eight were hereditary and one nonhereditary. Three pheochromocytomas had interstitial deletions that enabled us to localize the commonly deleted region as distal to D22S10 and proximal to D22S22. Hereditary pheochromocytoma frequently occurs in association with medullary thyroid carcinoma (MTC). Therefore, we also studied allelic loss on 22q in 23 hereditary MTCs. Only one of the MTCs showed LOH on 22q. Recent studies have mapped tumor suppressor loci associated with meningioma and neurofibromatosis type 2 (NF2) to 22q. The commonly deleted region in pheochromocytoma found by us encompasses the regions to which tumor suppressor genes associated with NF2 and meningioma have been mapped. The exact role of the pheochromocytoma tumor suppressor gene on 22q and its relationship to the suppressor genes involved in NF2 and meningioma remain unknown. © 1992 Wiley‐Liss, Inc.
Detection of 1p36 deletions in paraffin sections of neuroblastoma tissues
Authors: Stock Cornelia , Ambros Inge M. , Mann Georg , Gadner Helmut , Amann Gabriele , Ambros Peter F.
Published: February 2007

Nonradioactive in situ hybridization (NISH) on sections of paraffin‐embedded neuroblastoma tissue was performed to evaluate numerical and structural aberrations of chromosome 1. Two biotinylated probes specific for the heterochromatic (D1Z1) and subtelomeric regions of chromosome 1 (D1S32) were used to study normal tissue and 4 neuroblastoma samples with and without 1p36 deletions. The NISH findings in 3 of the 4 neuroblastomas correlated well with the results obtained by cytogenetic banding analysis. In 1 tumor sample, however, a deletion at 1p36 was observed by NISH, both on metaphase spreads and interphase nuclei, but not by cytogenetics. The NISH method is therefore advantageous when only paraffin‐embedded material is available and can be even more sensitive than conventional cytogenetic analyses under certain conditions. Moreover, the technique provides morphological information that cannot be obtained by methods relying on tissue extracts or cell suspensions. © 1993 Wiley‐Liss, Inc.
Molecular analysis of a variant 18;22 translocation in a case of lymphocytic lymphoma
Authors: Seité Paule , Leroux Dominique , Hillion Josette , Monteil Michèle , Berger Roland , Mathieu‐Mahul Danièle , Larsen Christian‐Jacques
Published: February 2007

We previously reported a 5′ rearrangement of the BCL2 locus in a t(18;22) variant translocation found in a lymphocytic lymphoma. Primary structure analysis of both rearranged chromosomes confirmed the localization of the breakpoint in the so‐called vcr region (for variant cluster region) that encompasses Z‐DNA stretches 5′ of the BCL2 locus, and in between Jλ1 and Cλ1 segments on the IGL locus. A 1,027 nucleotide segment from chromosome 22 was repeated on both derivative chromosomes 18q + and 22q ‐. This segment contained an octanucleotide that was also present in the normal chromosome 18 close to the breakpoint. As a consequence of the translocation, a normal‐sized BCL2 transcript was overexpressed in tumor cells. © 1993 Wiley‐Liss, Inc.
Deletion 9p22‐pter and loss of Y as primary chromosome abnormalities in a squamous cell carcinoma of the vocal cord
Authors: Worsham Maria J. , Benninger Michael J. , Zarbo Richard J. , Carey Thomas E. , Van Dyke Daniel L.
Published: February 2007

Loss of distal 9p is a common genetic alteration in squamous cell carcinoma of the head and neck. A vocal cord lesion incorporating a carcinoma‐in‐situ and a focus of invasive carcinoma revealed loss of the Y chromosome and a 9p22 rearrangement with loss of 9p22‐pter. Loss of 9p22‐pter appears to be a primary autosomal abnormality in this squamous cell carcinoma. © 1993 Wiley‐Liss, Inc.
Rearrangement of band q13 on both chromosomes 12 in a periosteal chondroma
Authors: Mandahl Nils , Willén Helena , Rydholm Anders , Heim Sverre , Mitelman Felix
Published: February 2007

Cytogenetic analysis of a recurrent periosteal chondroma revealed nonreciprocal translocations of both chromosomal segments 12q13→qter, from one chromosome 12 to 7q32 and from the homologous chromosome 12 to 16q22. The remaining parts of the two chromosomes 12 formed a dicentric chromosome. This is the second reported chondroma with a 12q13‐15 rearrangement, and changes of this chromosome region consequently seem to be nonrandom occurrences in chondromas. © 1993 Wiley‐Liss, Inc.
Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2
Authors: Mulligan Lois M. , Gardner Emily , Smith Barbara A. , Mathew Chris G. P. , Ponder Bruce A. J.
Published: February 2007

Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome arising from mutation at a locus or loci in chromosome region 10p11.2‐q11.2. The disease is characterized by medullary thyroid carcinoma (MTC) and pheochromocytoma (Pheo). To assess the genetic events in tumour initiation and progression in this disease, we have compiled an allelotype for MTC and Pheo tumours using polymorphic marker loci from each chromosome arm. Using a panel of 58 tumours, we found frequent allele losses on chromosome arms 1p (42%), 3p (30%), 3q (38%), 11p (11%), 13q (10%), 17p (8%), and 22q (29%). Loss of heterozygosity (LOH) for loci on chromosome 10 was detected in a single tumour where one whole chromosome copy was lost. We used a panel of polymorphic markers for each of chromosomes 1, 3, 11, and 17 to define a shortest region of overlap for these regions. The most frequent allele losses were on chromosome 1, spanning the entire short arm of the chromosome but not loci on 1q. LOH on chromosome 3 encompassed a minimal common region of 3q12‐qter. The regions of allelic deletion on chromosome 11(11pter‐p13), 17(17pter‐p11.2), and 13 (13q) encompass known tumour suppressor loci (WTI, TP53, RBI) which must therefore be candidates for genes contributing to MTC and Pheo development. Our data suggest allele loss on chromosome 11, 13, or 17 occurs predominantly in tumours with losses on chromosome 3, potentially reflecting the accumulation of genetic change in tumour progression. These events may be associated with more advanced disease in MTC. We suggest that at least 7 genes contribute to tumour development in MEN 2, including an initiating locus on chromosome 10 and loci on chromosomes 1, 3, 11, 13, 17, and 22 which have a progressional role in these tumours. © 1993 Wiley‐Liss, Inc.
Chromosome aberrations in tenosynovial giant cell tumors and nontumorous synovial tissue
Authors: Mertens Fredrik , Örndal Charlotte , Mandahl Nils , Heim Sverre , Bauer Henrik F. C. , Rydholm Anders , Tufvesson Arne , Willén Helena , Mitelman Felix
Published: February 2007

Five tenosynovial giant cell tumors—4 pigmented villonodular synovitis (PVNS) and 1 nodular tenosynovitis (NTS)—were investigated cytogenetically. Clonal chromosome aberrations were detected in 3 of them. One PVNS had t(7;16)(q22;q24) as the sole anomaly, whereas 1 PVNS and the NTS displayed aberrations suggesting clonal evolution: t(1;19)(p11;p12)/t(1;19), + 12 and ins(5;1)(q31;p13p34)/ins(5;1),t(2;4)(p23;q21), respectively. Including our 3 cases, a total of 6 tenosynovial giant cell tumors with karyotypic changes have been reported. Apart from 2 PVNS with trisomies 5 and 7, and 2 NTS with rearrangement of chromosome band 1p13, no recurrent chromosome change has been detected. Although the detection of clonal, acquired chromosome abnormalities has formerly generally been accepted as sufficient to conclude that a lesion is neoplastic, the interpretation of the pathogenetic significance of the karyotypic aberrations in synovial tumors is obscured by the fact that we have also detected comparable aberrations in obviously nonneoplastic synovial tissue. One of 2 lesions from patients with hemorrhagic synovitis carried a clonal del(13)(q12q21), and 2 of 4 synovectomy samples from patients with rheumatoid arthritis displayed –Y and –Y together with +7. The available cytogenetic data therefore cannot be used to resolve the controversy as to whether tenosynovial giant cell tumors are truly neoplastic or only reactive, inflammatory proliferations. © 1993 Wiley‐Liss, Inc.
Chromosome 12‐containing markers, including two dicentrics, in three i(12p)‐negative testicular germ cell tumors
Authors: Atkin Niels B. , Fox Margaret F. , Baker Marion C. , Jackson Zoè
Published: February 2007

A chromosome 12‐derived marker was seen in each of 3 testicular germ cell tumors that lacked the i(12p). An interesting feature of 2 of the markers was that the major part, including the centromere, of an acrocentric (a #13 and #14, respectively) was translocated onto 12p, resulting in a dicentric. In the third tumor, 13q (translocated onto 12q) was again probably involved in the rearrangement. The findings support the view that the amplification of genes on 12p represents a significant step in the development of germ cell tumors. © 1993 Wiley‐Liss, Inc.