bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X;autosome translocations
Authors: Dijkhuizen T. , van den Berg E. , Wilbrink M. , Weterman M. , van Kessel A. Geurts , Störkel S. , Folkers R. P. , Braam A. , de Jong B. 
Published: February 2007

AbstractSeveral human renal cell carcinomas with X;autosome translocations have been reported in recent years. The t(X;1)(p11.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translocation form a distinct subgroup of RCC. Here we report two new cases, one with a t(X;10)(p11.2;q23), the other with a t(X;1)(p11.2;p34). The common breakpoint in Xp11.2 suggests that they belong to the above‐mentioned subset of RCC. Using FISH in conjunction with X‐specific YAC clones, we demonstrate that the two new cases exhibited distinct breakpoints within Xp11.2.
Molecular and cytogenetic analysis of chromosome 7 in uterine leiomyomas
Authors: Ishwad C. S. , Ferrell R. E. , Davare J. , Meloni A. M. , Sandberg A. A. , Surti U. 
Published: February 2007

AbstractUterine leiomyomas are benign tumors that arise clonally from smooth muscle cells of the myometrium. Cytogenetic studies of uterine leiomyomas have shown that about 40% have chromosome abnormalities and that deletion of 7q is a common finding. The observations suggest the possible location of a growth‐suppressor gene within the 7q21‐q22 region. Molecular genetic analysis of cytogenetically normal tumors has frequently shown somatic loss of specific tumor suppressor genes detected by loss of heterozygosity in the critical region. To test the hypothesis that chromosome region 7q21‐q22 contains a growth‐suppressor gene involved in the development of leiomyomas, we examined 92 leiomyomas for allelic loss of 7q markers spanning the cytogenetically defined critical region. Forty tumors with cytogenetically defined 7q deletion, 45 tumors without cytogenetically visible 7q deletion, and seven tumors with no cytogenetic information were examined for allelic loss of loci D7S489, D7S440, D7S492, D7S518, D7S471, D7S466, and D7S530. Loss of heterozygosity for one or more of these loci was observed in 23 of 40 (57.5%) of the tumors with deletion of 7q and in 2 of 45 cases without a cytogenetically visible deletion. The tumors with cytogenetic deletion of 7q, but no loss of 7q21‐q22 markers, were mosaics, with only a minority of cells containing the cytogenetic deletion. The critical region of loss is defined by the markers D7S518 and D7S471, each showing loss in approximately 50% of informative cases. These markers define a 10 cM region of 7q21‐q22 that is consistent with the cytogenetically defined smallest region of overlap and exclude loss of the MET oncogene locus and WNT1, the murine mammary tumor‐virus integration site, from the critical region. Our results further define a region that is consistently lost in leiomyomas with cytogenetic deletion of chromosome arm 7q. This region may contain a tumor suppressor gene involved in the development of a subset of leiomyomas.
Regional fine mapping of the multiple‐aberration region involved in uterine leiomyoma, lipoma, and pleomorphic adenoma of the salivary gland to 12q15
Authors: Wanschura S. , Kazmierczak B. , Schoenmakers E. , Meyen E. , Bartnitzke S. , van de Ven W. , Bullerdiek J. , Schloot W. 
Published: February 2007

AbstractCytogenetic aberrations involving 12q13‐15 are frequently observed in a variety of benign solid tumors. Using a chromosome walking approach combined with fluorescence in situ hybridization analysis, we were able to show that the chromosome 12 breakpoints involved in uterine leiomyoma, pleomorphic adenoma of the salivary gland, and lipoma cluster to the same chromosomal region, which we therefore designated MAR (multiple‐aberration region). By comparing the G‐banding pattern of prometaphase chromosomes of amniotic fluid cells and lymphocytes to the position of hybridization signals obtained with a cosmid pool encompassing this breakpoint hot spot region, MAR was assigned to 12q15. We conclude that, despite the cytogenetic breakpoint assignment to the three bands 12q13‐15 in individual uterine leiomyomas, lipomas, and pleomorphic adenomas of the salivary glands in the past, most likely 12q15 is the only 12q breakpoint site in these three distinct solid tumor types.
Genetic instability of chromosome 3 in HPV‐immortalized and tumorigenic human keratinocytes
Authors: Montgomery Karen Dyer , Tedford Karen L. , McDougall James K. 
Published: February 2007

AbstractThe HPV‐1811 cell line is derived from primary human foreskin keratinocytes that have been transfected with human papilloma virus type 18. At late passage, these cells produce invasive squamous cell carcinomas when injected into nude mice. A striking, but unstable, aberration of chromosome 3 occurs very early after establishment of the culture; a consistent rearrangement is observed concomitant with tumorigenicity. Using molecular cytogenetic techniques, we characterized the complex development of this aberration. A whole chromosome probe to this chromosome was made by linker‐adapter PCR amplification of a single flow‐sorted chromosome. Hybridization of this probe to normal metaphase chromosomes revealed the der (3) to be composed of chromosome 3, distal 13q, and 21q22. Hybridization of a 3q subtelomeric probe and a glycoprotein V probe which maps to 3qter indicated that this locus is duplicated in the final form of the chromosome, but that much instability occurs prior to its establishment. The ETS2 oncogene, which maps to 21q22, is translocated to the der(3) when the cell line becomes tumorigenic, but not prior to this time. Early‐passage cells which have been induced to become tumorigenic by exposure to the carcinogen nitrosomethylurea also have the localization of the ETS2 at 3qter.
Genetic analysis of chromosome 13 deletions in BCR/ABL negative chronic myeloproliferative disorders
Authors: Pastore Cristina , Nomdedeu Josep , Volpe Gisella , Guerrasio Angelo , Cambrin Giovanna Rege , Parvis Guido , Pautasso Marisa , Daglio Cristiano , Mazza Umberto , Saglio Giuseppe , Gaidano Gianluca 
Published: February 2007

AbstractChromosomal deletions of band 13q14 occur recurrently in BCR/ABL negative chronic myeloproliferative disorders (CMPD), including myelosclerosis with myeloid metaplasia (MMM), polycythemia vera (PV), essential thrombocythemia (ET), juvenile chronic myeloid leukemia (JCML), and the so‐called BCR/ABL − chronic myeloid leukemia (CML). The RB1 tumor suppressor locus, mapping to 13q14, has long since been hypothesized as the important gene. In this report, we have determined the frequency of 13q14 deletions at the molecular level in a large panel of BCR/ABL − CMPD at different disease stages and performed a detailed genetic analysis of gross rearrangements/deletions and point mutations of the RBI gene in these disorders. Our data show that molecular deletions of 13q14 are detected in a relatively large fraction of BCR/ABL − CMPD (38%), that they appear to be more frequent in MMM than in other BCR/ABL − CMPD, and that they may be present at diagnosis or occur during blastic evolution of the neoplasia. The RBI gene displayed a germline configuration in all BCR/ABL − CMPD tested, suggesting that 13q14 deletions in these disorders affect a tumor suppressor locus distinct from RB1.
Localization of metastasis suppressor gene(s) for rat prostatic cancer to the long arm of human chromosome 10
Authors: Nihei Naoki , Ichikawa Tomohiko , Kawana Youko , Kuramochi Hiroaki , Kugo Hiroyuki , Oshimura Mitsuo , Killary Ann M. , Rinker‐Schaeffer Carrie W. , Barrett J. Carl , Isaacs John T. , Shimazaki Jun 
Published: February 2007

AbstractTo examine the role of human chromosome 10 in development of prostatic cancer, we introduced human chromosome 10 into highly metastatic rat prostatic cancer cells by microcell‐mediated chromosome transfer. Microcell hybrid cells introduced with human chromosome 10 showed suppression of the metastatic ability to the lung to some extent without any suppression of tumorigenicity, although the tumor growth rate decreased slightly. To minimize the region that contains metastasis suppressive activity, the hybrid cells in metastasis foci of lung were established in culture and reanalyzed for portions of human chromosome 10 retained in the metastasis tissues. Cytogenetic and molecular analyses demonstrated that loss of the region between 10cen and D10S215 on human chromosome arm 10q was related to expression of the metastatic phenotype. These results demonstrate that the region between 10cen and D10S215 on human chromosome arm 10q contains at least one of the metastasis suppressor genes for rat prostatic cancer.
Normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cell line SiHa
Authors: Uejima Hiroshi , Mitsuya Kohzoh , Kugoh Hiroyuki , Horikawa Izumi , Oshimura Mitsuo 
Published: February 2007

AbstractFor identification of the chromosome carrying cellular senescence‐inducing activity, normal human chromosome 2, 3, 6, 7, 9, 11, or 12 tagged with a selectable marker gene (neo) was introduced into the human cervical carcinoma cell line SiHa via microcell‐mediated chromosome transfer. Seventy‐six percent (158/207) of the G418‐resistant clones obtained by the transfer of chromosome 2 showed a remarkable change in morphology (cells were flat), and 93% (147/158) of them ceased to divide (senesced) prior to 6–9 population doublings, whereas most of the clones generated by the transfer of other chromosomes exhibited a morphology similar to that of the parental cells and continued to grow. Chromosome analyses suggested that cells which escaped from senescence contained only a small fragment derived from the transferred chromosome 2, whereas the transferred chromosomes were apparently intact in most of the continuously growing microcell hybrids with introduction of other chromosomes. These results indicate that the normal human chromosome 2 carries a gene or genes that induce cellular senescence in SiHa cells.
Microsatellite instability in endometrial carcinomas: Frequent replication errors in tumors of early onset and/or of poorly differentiated type
Authors: Kobayashi Kanji , Sagae Satoru , Kudo Ryuichi , Saito Hiroko , Koi Sumiko , Nakamura Yusuke 
Published: February 2007

AbstractEndometrial and ovarian carcinomas are common among women belonging to hereditary nonpolyposis colorectal carcinoma (HNPCC) families; tumors developing in them are characterized by genetic instability due to an inherited dysfunction of the DNA‐mismatch‐repair system. To clarify the role of similar genetic factors in sporadic forms of gynecological tumors, we examined 77 endometrial and 68 ovarian carcinomas for replication error (RER) at five microsatellite loci. RER‐positive phenotypes at two or more microsatellite loci were observed in 18 of the endometrial carcinomas, but in only two of the ovarian carcinomas. Among the patients with endometrial carcinomas, the frequency of RER tended to be higher in those under age 50 than in those over age 60. Furthermore, RER was significantly more frequent in poorly differentiated than in well‐differentiated tumors (P = 0.008, Fisher's exact test). These data suggest that genetic factors characterized by RER are likely to play an important role in some endometrial carcinomas, particularly those of early onset and/or of the poorly differentiated type.
Allelic loss in squamous cell carcinomas of the larynx: Discordance between primary and metastatic tumors
Authors: Sun Paul C. , El‐Mofty Samir K. , Haughey Bruce H. , Scholnick Steven B. 
Published: February 2007

AbstractThe mutational inactivation of suppressor genes, a process required for cancer progression, generates new genetic subclones within a tumor. The allelic losses that frequently unmask these mutations serve not only as markers of the chromosomal locations of these genes but also as clonal fingerprints of the shifting relationships between these genetically heterogeneous cell populations. The rise of the metastasis‐competent subclone to dominance within the primary tumor should be reflected in the similarity of the genetic fingerprints of the primary tumor and its resultant metastases. We have tested this hypothesis by comparing the patterns of allelic loss of individual primary laryngeal squamous cell carcinomas and their resultant cervical lymph node metastases at 16 different genetically polymorphic loci on 15 chromosome arms. Although primary tumors and metastases both frequently lose heterozygosity on the same chromosome arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their primary tumors at one or two of the loci examined. Discordance between the two tumor cell populations from the same patient is suggestive of either subclone heterogeneity within the primary tumor at the time of establishment of the metastasis or further clonal evolution of both tumors after metastasis.
Deletion of 1p loci and microsatellite instability in colorectal polyps
Authors: Lothe Ragnhild A. , Andersen Solveig Norheim , Hofstad Bjørn , Meling Gunn Iren , Peltomäki Päivi , Heim Sverre , Brøgger Anton , Vatn Morten , Rognum Torleiv O. , Børresen Anne‐Lise 
Published: February 2007

AbstractPrevious cytogenetic studies have indicated that a subset of large bowel adenomas have distal 1p deletions. We addressed this question by examining 70 sporadic polyps (63 adenomas, 5 hyperplastic polyps, and 2 polyps of undetermined histology) from 55 patients for alterations at eight loci on the short arm of chromosome 1 and found allele imbalance (A1) or loss of one allele (LOH) in 14 (20%). The locus most frequently changed was MS1, which maps to 1p33‐35. Fluorescence in situ hybridisation with centromeric and telomeric probes for chromosome 1, performed for 11 polyps, did not yield an abnormal number of signals, in accordance with the interpretation that the observed A1 and LOH were the result of interstitial deletions in 1p. Whereas allelic imbalance at five other loci (mapping to 5q, 8p, 10p, 11p and 17q) was found less frequently, and then mainly in large (> 2 cm) tumours, the 1p alterations were equally distributed among small (< 1 cm) and large polyps. They were preferentially found in left‐side tumours. Instability at microsatellite loci—the mutator phenotype—is demonstrated by shifts in the electrophoretic mobility of normal alleles. The mutator phenotype was first associated with hereditary nonpolyposis colorectal cancer but is also occasionally found in sporadic colorectal carcinomas; however, it is still uncertain when in the adenoma‐carcinoma sequence in this type of genomic instability arises. We therefore looked for it at 12 dinucleotide repeat loci and found that seven tumours (six adenomas and one hyperplastic polyp) from seven patients had acquired new alleles not seen in the patients' corresponding normal DNA. Our results suggest that inactivation of a putative suppressor gene distally in chromosome arm 1p is an early event in colorectal tumourigenesis. They also show that microsatellite instability can be detected in large bowel polyps, indicating that this phenomenon, too, probably plays a pathogenic role for some colorectal tumours early in the adenoma‐carcinoma sequence.
Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas
Authors: Bartsch Detlef , Shevlin Douglas W. , Tung William S. , Kisker Oliver , Wells Samuel A. , Goodfellow Paul J. 
Published: February 2007

AbstractThe gene encoding the cell‐cycle regulatory protein p16, CDKN2, is localized on chromosome band 9p21. CDKN2 is frequently deleted or mutated in a variety of tumor cell lines, including pancreatic cancer cell lines and xenografts, as well as in some primary tumors. We examined 32 primary pancreatic adenocarcinomas for CDKN2 mutations and for loss of heterozygosity of 9p21 sequences to assess the role of CDKN2 in pancreatic carcinogenesis. Single‐strand conformation variant analysis (SSCV) and direct sequencing of the variants revealed somatic CDKN2 mutations in 11 of 32 tumors (five frame‐shift mutations, five nonsense mutations, and one missense mutation). One tumor appeared to be characterized by homozygous deletion of CDKN2. These results suggest that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas.
Co‐amplification and concomitant high levels of expression of a DEAD box gene with MYCN in human neuroblastoma
Authors: Manohar Chitra F. , Salwen Helen R. , Brodeur Garrett M. , Cohn Susan L. 
Published: February 2007

AbstractMYCN gene amplification is strongly correlated with poor prognosis in neuroblastoma (NB), the second most common solid pediatric tumor. However, increased MYCN expression seen in tumors that lack MYCN amplification does not correlate with aggressive clinical behavior. Whereas the MYCN gene spans only 7 kb, the MYCN amplicon has been shown to range in size from 350 kb to more than 1 Mb. Given the large size of the amplicon, it is possible that additional genes are co‐amplified in NBs whose expression may contribute to the aggressive phenotype associated with MYCN‐amplified tumors. We isolated a cDNA clone from a human NB library that is identical to DDX1, a gene recently reported to be preferentially expressed in two retinoblastoma cell lines that also express high levels of MYCN. DDX1 belongs to a family of genes that encode DEAD (Asp‐Glu‐Ala‐Asp) box proteins, putative ATP‐dependent RNA helicases implicated in a number of cellular processes involving alterations of RNA secondary structure. We examined the frequency of DDX1 amplification in 15 NB cell lines, 1 neuroepithelioma cell line, and 122 NB tumors by Southern blot analyses, and we found that 7 of 10 MYCN‐amplified cell lines and 27 of 40 (68%) MYCN‐amplified tumors also harbored multiple coples of the DDX1 gene. Amplification of DDX1 was associated with high levels of DDX1 mRNA expression in the NB cell lines and tumors as examined by Northern analysis. Neither DDX1 gene amplification nor enhanced expression was observed in tumors or cell lines that lacked MYCN amplification. Because RNA helicases play important roles in both post‐transcriptional and translational gene regulation, high levels of DDX1 expression consequent to genomic amplification may contribute to the malignant phenotype of a subset of NBs.
Partial chromosome 21 amplification in a child with acute lymphoblastic leukemia
Authors: Coniat Maryvonne Le , Romana Serge P. , Berger Roland 
Published: February 2007

AbstractMonosomy 21 and metacentric markers corresponding in size to chromosomes 8 to 12 were found as the only clonal chromosomal changes in a child with acute lymphoblastic leukemia (ALL). Chromosome painting with a whole chromosome 21‐specific probe showed that the marker originated from chromosome 21. Fluorescence in situ hybridization with yeast artificial chromosome (YAC) probes to chromosome 21 showed genomic amplification with two, four, or more copies of the probed DNA sequences present on the marker. The most amplified regions of chromosome 21 were centromeric and telomeric to the Down's syndrome region. This observation supports the notion that amplification of only parts of chromosome 21 may be important in the leukemogenic process in spite of the high incidence of complete trisomy 21 in ALL.
Identification of multiple chromosome 12 abnormalities in human testicular germ cell tumors by two‐color fluorescence in situ hybridization (FISH)
Authors: Smolarek Teresa A. , Blough Ruthann I. , Foster Richard S. , Ulbright Thomas M. , Palmer Catherine G. , Heerema Nyla A. 
Published: February 2007

AbstractThe distribution of segments of the short and long arms of chromosome 12 was distinguished by two‐color fluorescence in situ hybridization (FISH) in 27 cytogenetically abnormal testicular germ cell tumors (TGCTs). A 12p‐specific probe was developed by chromosomal microdissection and sequence‐independent polymerase chain reaction (PCR) amplification and was combined with a commercially available whole‐chromosome 12 painting probe. The TGCTs included both i(12p)‐positive and i(12p)‐negative primary tumors and lymph node metastases from patients in clinical stage I or stage II who were not previously treated with chemotherapy. Rearrangements of the short arm of chromosome 12 and overrepresentation of 12p DNA sequences were found in all cases. In addition, cryptic rearrangements of 12p were found in 39% (7/18) of the i(12p)‐positive tumors and in 78% (7/9) of the i(12p)‐negative tumors. Only 7% (2/27) of all tumors had cryptic rearrangements of 12q.
Germline mutations in the RB1 gene in patients with hereditary retinoblastoma
Authors: Liu Zaoxia , Song Yue , Bia Britta , Cowell John K. 
Published: February 2007

AbstractWe have analyzed the 27 exons and the promoter region of the RB1 gene in familial or sporadic bilateral retinoblastoma by using single‐strand conformation polymorphism analysis. For improvement over previous studies, a new set of primers has been designed, which allow for amplification of the coding and splicing sequences only. The positioning of the polymerase chain reaction (PCR) primers was such that the resulting PCR products were of different sizes, which enabled us to analyze two different exons simultaneously and still distinguish between the banding profiles for both (biplex analysis). By using this approach, we were able to identify mutations in 22 new patients, but the overall efficiency of the procedure when we used a single‐pass regimen was only 48%. The mutations were small insertions and deletions and point mutations in roughly equal proportions.
Characterization of regions of chromosomes 12 and 16 involved in nephroblastoma tumorigenesis
Authors: Austruy Estelle , Candon Sophie , Henry Isabelle , Gyapay Gabor , Tournade Marie‐France , Mannens Marcel , Callen David , Junien Claudine , Jeanpierre Cécile 
Published: February 2007

AbstractThere are at least three loci involved in Wilms' tumor (WT) tumorigenesis: WT1 in 11p13, WT2 in 11p15.5, and WT3, as yet unmapped. A compilation of cytogenetic data published for 107 WT revealed that deletion of chromosome 16 and duplication of chromosome 12 occur as frequently as the well‐documented 11p deletions. Allelic imbalance for chromosomes 16 and 12 was investigated in a series of 28 WT. By use of a large panel of restriction fragment length polymorphisms and (CA)n probes, we demonstrated loss of heterozygosity (LOH) for 16q in seven (25%) of the tumors. The whole length of 16q was involved in six of the tumors. Moreover, consistent with a previous report of 16q13 LOH in a sporadic WT and a constitutional breakpoint in a Beckwith‐Wiedemann patient, we map a region of particular interest to between D16S308 and D16S320. The assumption that 16q LOH may be an early event was based on: 1) the detection of 16q LOH in one case of nephroblastomatosis; 2) the presence of a complete (clonal) 16q LOH in a tumor with partial (mosaic) 11p LOH; and 3) 16q LOH as the sole abnormality in one WT. By quantification of chromosome 12 allelic imbalance, we detected duplication in 18% of the total series and in 25% of the sporadic unilateral cases. The common region extended from the centromere to D12S7 in 12q21.1‐q23. We also suggest that the various pathogenetically important loci are not equally involved in the different forms of WT and that their sequential involvement may differ.