DOCSLIB.ORG

Chromosome 8P Deletions Are Associated with Invasive Tumor Growth in Urinary Bladder Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chromosome 8P Deletions Are Associated with Invasive Tumor Growth in Urinary Bladder Cancer American Journal ofPathology, Vol. 151, No. 3, September 1997 Copynight © American Societyfor Investigative Pathology Chromosome 8p Deletions Are Associated with Invasive Tumor Growth in Urinary Bladder Cancer Urs Wagner,* Lukas Bubendorf,* a third locus telomeric to 8p23.1.912 Previous studies Thomas C. Gasser,t Holger Moch,* using molecular analysis and comparative genomic hy- Jean-Philippe Gorog,* Jan Richter,* bridization (CGH) have found 8p deletions in more than Michael J. Mihatsch,* Frederick M. Waldman, 25% of bladder tumors.57' 13 Chromosome 8 mapping by and Guido Sauter* Takle et al13 revealed common areas of deletion span- ning from 8p11.2 to 8p12 and from 8p21.1-8pter. In From the Institute ofPathology* and Urologic Clinics,t University another study, we found a strong association between ofBasel, Basel, Switzerland, and the Division ofMolecular chromosome 8q gains and histological phenotype, sug- Cytometry,* Department ofLaboratory Medicine, University of gesting that a gain of chromosome 8q material might also California, San Francisco, San Francisco, California contribute to bladder cancer progression.14 To better understand the role of chromosome 8 alter- ations in bladder cancer 87 tumor specimens were ex- Alterations of chromosome 8, including deletions of amined by dual labeling fluorescence in situ hybridization (FISH). aims were to and 8p, occur frequently in many tumors. In this study, Specific explore prevalence fluorescence in situ hybridization was used to study extent of chromosome 8p losses in bladder cancer and to the relationship between 8p deletions, 8q gains, and determine the relationship of chromosome 8p losses with tumor phenotype in bladder cancer. Celis from 87 tumors 8q gains and histopathologic phenotype. were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 Materials and Methods deletions and 8q24 gains were strongly associated Tumor Material with tumor phenotype. There was a marked differ- ence in 8p22 deletions between noninvasive (pTa) Seventy-two formalin-fixed, paraffin-embedded bladder tumors (3/33) and minimally invasive (pTl) tumors tumors were randomly selected from the archives of the (8/19; P = 0.005) whereas there was no significant Institute of Pathology, University of Basel. Nuclei of for- difference between pTl and muscle-invasive (pT2-4) malin-fixed tissue blocks were dissociated and dropped tumors (19/35; P = 0.3926). Six tumors with 8p22 onto slides as previously described.15 Additionally, im- deletion were examined at 8p12. Three of these tu- print preparations were made immediately after surgery mors showed no 8p12 deletion, narrowing down the from 15 unfixed bladder tumor samples and stored at site of a putative tumor suppressor gene distal to -20°C. All hematoxylin and eosin slides of each case 8pl2. In one other case, there was a marked increase were reviewed by a single pathologist (G. Sauter). Tumor in 8p12 copy number (>40 per cell; amplification), stage and grade were defined according to UICC and suggesting the presence of an oncogene involved in World Health Organization classifications.16,17 Particu- bladder cancer at 8p12. The marked difference in larly stringent criteria were applied for the diagnosis of 8p22 deletions between noninvasive (pTa) and mini- stage pTl, which is defined by a tumor invasion of the mally invasive (pTl) tumors is consistent with a role suburothelial stroma but not of the muscular bladder wall. of a putative tumor suppressor gene on 8p for devel- An unequivocal stromal invasion was required to prevent opment of invasive tumor phenotype. (AmJ Pathol overstaging of pTa tumors. To minimize the risk of under- 1997, 151:753-759) staging muscle-invasive tumors (pT2-T4), the presence of tumor-free fragments of the muscular bladder wall in Recent cytogenetic and molecular studies have shown that deletions involving the short arm of chromosome 8 Supported by Krebsforschung Schweiz, Schweizerische Krebsliga (SKL are frequent in numerous tumors including prostate,1 137-7-1995), Krebsliga Beider Basel, and Thurgauer Krebsliga (G. Sau- lung,2 colon,3,4 and bladder cancer.5 It has been sug- ter, T. C. Gasser, and M. J. Mihatsch) and National Institutes of Health gested that 8p may be the site of at least one tumor grant CA47537 (F. M. Waldman). suppressor gene.5'6 Mapping studies have proposed Accepted for publication June 18, 1997. several different loci as sites of putative tumor suppressor Address reprint requests to Dr. G. Sauter, Institut fOr Pathologie, Uni- genes, 9 including an area between 8p21.3 and versitatskliniken, Kantonsspital Basel, Schonbeinstrasse 40, CH-4003 8p22,231011 another region centromeric to 8p21,4 and Basel, Switzerland. 753 754 Wagner et al AJP September 1997, Vol. 151, No. 3 the primary biopsy, and the absence of muscle invasion were counted for 100 nuclei. To avoid misinterpretation in a subsequent transurethral resection performed within due to insufficient hybridization efficiency, cells were 8 weeks after the first biopsy was required. Muscle inva- scored only when at least one bright P1 and one bright sion in a follow-up biopsy after less than 8 weeks was centromere signal were present. Two P1 signals were considered to indicate a sampling error at the initial bi- counted as one signal when they were situated very close opsy. Because of the limitations of transurethral biopsies to each other (O0.5 p.m) to avoid misinterpretation due to in accurately determining the depth of invasion of higher- sister chromatids of cells in S or G2M phase. The defini- stage bladder cancer, all tumors showing muscle inva- tions used for deletions and gains of loci were based on sion were categorized into one group (pT2-T4). Only the results obtained in normal urothelial cells from 10 tumors for which histological staging was unequivocal patients without a bladder cancer history (mean + 3 SD). were included in the study. DNA Probes for FISH Statistics A chromosome 8 centromere probe (pJM12) was used x2 tests were used to compare the frequency of genomic in combination with P1 probes mapping to 8p22 alterations between tumors of different grades and (RMC08POO5, LPL, Flpter 0.140), 8p12 (RMC08PO03, stages and to evaluate the relationship between 8p de- D8S549, Flpter 0.307), 8q12 (RMC08PO02, D8S285, letions and 8q gains. Flpter 0.420), and 8q24 (RMC08POO1, c-myc, Flpter 0.845) to determine gains and deletions of chromosome 8 sequences. All probes were kindly provided by Dr. Joe Gray, Resource for Molecular Cytogenetics, University of Results California, San Francisco. The centromere 8 probe was labeled with biotin-14-dATP and P1 probes were labeled Pathology with digoxigenin-1 1-dUTP by nick translation using stan- Eighty-seven primary bladder tumors (72 paraffin-disso- dard protocols. ciated and 15 fresh touch preparations) were success- fully analyzed by FISH (17 additional dissociated cases Fluorescence in Situ Hybridization had insufficient hybridization intensity and were exclud- ed). Thirty-three tumors were confined to the bladder In all hybridizations, a chromosome 8 centromere probe mucosa (pTa), nineteen showed invasion of the lamina (pJM12) was simultaneously used with a locus-specific propria (pTl), and thirty-five were muscle invasive (pT2- P1 probe to define relative gains and losses. FISH was as T4). Fourteen tumors were classified as grade 1, thirty- previously described.18 Briefly, cells on slides were de- nine were grade 2, and thirty-four were grade 3. natured in 70% formamide/2X SSC (1X SSC is 0.15 mol/L NaCI, 0.015 mol/L sodium Citrate), pH 7, at 75°C for 2.5 minutes. After dehydration in graded ethanol, samples were treated with proteinase K (Sigma Chemical Co., St. Normal Controls Louis, MO; 2.0 ,ug/ml for formalin-fixed cells and 0.2 Ten tissue samples (three unfixed bladder washes and ,ug/ml for unfixed specimens) in PBS (pH 7.0) for 7 min- dissociated nuclei from seven formalin-fixed biopsies) utes at 37°C, followed by ethanol dehydration. The hy- containing normal urothelial cells from patients without a bridization mixture was denatured for 5 minutes at 750C. bladder cancer history were used as normal controls. All A 10-,ul aliquot of hybridization mixture consisted of 10 ng normal controls showed an equal number of centromere of P1 probe, 30 ng of centromere 8 probe, and 10 ng of and P1 signals in .85% of cells. The fraction of cells with unlabeled, sonicated (200- to 500-bp) human placental fewer P1 signals than centromere signals ranged from 0 DNA (Sigma) in 50% formamide, 10% dextran sulfate, to 14% (7.5 ± 5.2, mean ± SD). These cells were attrib- and 2X SSC (pH 7). Re-annealing of hybridization mixture uted to a decreased hybridization efficiency of the small was allowed for 30 minutes at 37°C. Hybridization was P1 probes as compared with the much larger centromere overnight at 37°C. Lymphocyte metaphase spreads were probes. The fraction of cells with more P1 signals than used to assure probe specificity. The slides were washed centromere signals (considered to represent cells in S or in 50% formamide/2X SSC, pH 7, at 450 C. Immunohis- G2 phase with both sister chromatids visible) was gen- tochemical probe detection using Texas Red avidin (Vec- erally lower than the fraction of cells with deletion and tor Laboratories, Burlingame, CA) and FITC-conjugated ranged from 0 to 10% (4.5 ± 3.1, mean ± SD). Our cutoff sheep anti-digoxigenin (Vector) was as described.18 Nu- levels for definition of deletions and gains on a tumor clei were counterstained with 0.07 ptg/ml 4.5-diamino-2- basis were based on these results (mean number of phenyl-Indole (DAPI) in antifade solution. aberrant cells found in normal tissues + 3 SD). More than 25% of cells with fewer P1 signals than centromere 8 Scoring of FISH Signals signals were required to define a tumor as deleted for a specific locus.
Load more

Recommended publications
  • Pathogenetics. an Introductory Review
    The Egyptian Journal of Medical Human Genetics (2016) 17, 1–23 HOSTED BY Ain Shams University The Egyptian Journal of Medical Human Genetics www.ejmhg.eg.net www.sciencedirect.com REVIEW Pathogenetics. An introductory review Mohammad Saad Zaghloul Salem 1 Faculty of Medicine, Ain-Shams University, Cairo, Egypt Received 1 July 2015; accepted 7 July 2015 Available online 27 July 2015 KEYWORDS Abstract Pathogenetics refers to studying the different aspects of initiation/development/progres Pathogenetics; sion and pathogenesis of genetic defects. It comprises the study of mutagens or factors capable Mutagens; of affecting the structural integrity of the genetic material leading to mutational changes that, in Mutation; the majority of cases, result in harmful effects due to the resulting disturbances of functions of Pathogenetic mechanisms; mutated components of the genome. The study of mutagens depicts different types of mutagenic Anti-mutation mechanisms factors, their nature, their classification according to their effects on the genetic material and their different modes of action. The study of mutation involves different types of mutations classified according to various parameters, e.g. magnitude, severity, target of mutational event as well as its nature, which can be classified, in turn, according to whether it is spontaneous or induced, static or dynamic, somatic or germinal mutation etc. Finally, pathogenetics comprises studying and delin- eating the different and innumerable pathophysiological alterations and pathogenetic mechanisms that are directly and indirectly involved in, and leading to, the development of genetic disorders, coupled with a parallel study of various anti-mutation mechanisms that play critical roles in minimizing the drastic effects of mutational events on the genetic material and in effective protection against the development of these diseases.
    [Show full text]
  • But Broke Down More Frequently Than Those Stabilised by Natural Degree
    HYBRIDITY SELECTION IN CAMPANULA C. D. DARLINGTON and L. F. LA COUR John Innes Horticultural Institution, Bayfordbury, Hert ford, Herts. Received25.Viii.49 CONTENTS I. Introduction . .217 2. Building Newlypes . .218 3. Ring-Formation and the Hybridity Optimum . .219 4. Analytic Crosses . .222 5. Unbalanced Types . .224 6. Fertility and the Breeding System . .226 7. New Interchanges . .227 8. The Stable Telocentric . .228 9. Telocentrics and Interchanges . 230 10. A Monosomic Plant . 231 II. New Telocentrics and Isochromosomes . .233 12. The Origin of lsochromosomes . .237 13. Pollen-Grain Inheritance . .239 14. The Future of lsochromosomes . .240 IS. The Evolution of Chromosome Numbers . 241 16. Conclusions . .242 17. Summary . 243 18. References . .246 Appendix: Compound Constrictions by L. F. La Cour 243 I. INTRODUCTION INour first account of ring formation in Campanula persicfo1ia (Gairdner and Darlington, 1931)weshowed how mechanical rules could be applied for the construction of plants with large rings at meiosis by the combination of interchanged chromosomes found in wild races. In our second account (Darlington and Gairdner, 1937)weshowed how large rings were maintained by the elimination of homozygotes but broke down more frequently than those stabilised by natural selection in Oenothera, owing to the occurrence of crossing-over between interstitial segments in opposite complexes. We also showed the high degree of structural hybridity in regard to inversions which was correlated with interchange hybridity in a cross-fertilising species. Our present object is to make use of the interchanges and other break- ages as markers in determining how hybridity is maintained by selection in the species, in other words how the breeding system works.
    [Show full text]
  • Chromosome 18
    Chromosome 18 Description Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 18, one copy inherited from each parent, form one of the pairs. Chromosome 18 spans about 78 million DNA building blocks (base pairs) and represents approximately 2.5 percent of the total DNA in cells. Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 18 likely contains 200 to 300 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body. Health Conditions Related to Chromosomal Changes The following chromosomal conditions are associated with changes in the structure or number of copies of chromosome 18. Distal 18q deletion syndrome Distal 18q deletion syndrome occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "distal" means that the missing piece (deletion) occurs near one end of the chromosome arm. The signs and symptoms of distal 18q deletion syndrome include delayed development and learning disabilities, short stature, weak muscle tone ( hypotonia), foot abnormalities, and a wide variety of other features. The deletion that causes distal 18q deletion syndrome can occur anywhere between a region called 18q21 and the end of the chromosome. The size of the deletion varies among affected individuals. The signs and symptoms of distal 18q deletion syndrome are thought to be related to the loss of multiple genes from this part of the long arm of chromosome 18.
    [Show full text]
  • Frequent Multiplication of the Long Arm of Chromosome 8 in Hepatocellular Carcinoma1
    [CANCER RESEARCH 53. 857-860. February 15. 1993] Frequent Multiplication of the Long Arm of Chromosome 8 in Hepatocellular Carcinoma1 Yoshiyuki Fujiwara, Monto Monden, Takesada Mori, Yusuke Nakamura,2 and Mitsuru Emi Department of Biochemistry ¡Y.F., Y. N.. M. E.l. Cancer Institute. 1-37-1 Kaini-lkebukuro. Tiishinia-ku. Tokyo 170. and the Second Department of Surgen' ¡Y.F.. M. M., T. M.], Osaka University MédiraiSellimi. 1-1-50 Fukushima. Fukushima, Osaka 53}, Japan ABSTRACT normal and tumor DNAs enabled visualization of subtle changes that had occurred in tumor DNAs. Frequent allelic losses at loci on several chromosomes have been de We initiated a systematic RFLP analysis of paired DNAs from tected in human hepatocellular carcinomas, but other types of chromo HCCs and their corresponding normal tissues to examine whether somal abnormalities have not been characterized well. Using eight poly multiplication of chromosomal segments may take place during de morphic DNA markers on chromosome 8, we examined 120 primary hepatocellular carcinomas for abnormalities in the copy number of these velopment of HCC. In this paper, we present results of RFLP analysis loci in tumor cells. A 2- to 6-fold increase in intensities of bands repre at loci on chromosome 8, and we demonstrate that multiplication of senting single alíeleswas observed in 32 of the 78 tumors that were single alíeleson part or all of the long arm of chromosome 8 has informative for one or more of the markers, indicating an increase in copy occurred in a large proportion of HCCs. number ("multiplication") of alíeleson8q.
    [Show full text]
  • A Study on Acute Myeloid Leukemias with Trisomy 8, 11, Or 13, Monosomy 7, Or Deletion 5Q
    Leukemia (2005) 19, 1224–1228 & 2005 Nature Publishing Group All rights reserved 0887-6924/05 $30.00 www.nature.com/leu Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q C Schoch1, A Kohlmann1, M Dugas1, W Kern1, W Hiddemann1, S Schnittger1 and T Haferlach1 1Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany We performed microarray analyses in AML with trisomies 8 aim of this study to investigate whether gains and losses on the (n ¼ 12), 11 (n ¼ 7), 13 (n ¼ 7), monosomy 7 (n ¼ 9), and deletion genomic level translate into altered genes expression also in 5q (n ¼ 7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of other areas of the genome in AML. genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained Materials and methods chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted Samples regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed Bone marrow samples of AML patients at diagnosis were over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes analyzed: 12 cases with trisomy 8 (AML-TRI8), seven with characteristic for AML with 5q deletion and monosomy 7 are trisomy 11 (AML-TRI11), seven with trisomy 13 (AML-TRI13), located on chromosomes 5 or 7.
    [Show full text]
  • 8 Translocation in Burkitt Lymphoma Interrupts the VK Locus (Gene Localization/Immunoglobulin Genes/Genetics of B-Cell Neoplasia/In Situ Hybridization) BEVERLY S
    Proc. Natl. Acad. Sci. USA Vol. 81, pp. 2444-2446, April 1984 Genetics The 2p breakpoint of a 2;8 translocation in Burkitt lymphoma interrupts the VK locus (gene localization/immunoglobulin genes/genetics of B-cell neoplasia/in situ hybridization) BEVERLY S. EMANUEL*, JULES R. SELDENt, R. S. K. CHAGANTIt, SURESH JHANWARt, PETER C. NOWELL, AND CARLO M. CROCEt§ *Departments of Pediatrics and of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, and tThe Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia, PA 19104; and MLaboratory of Cancer Genetics and Cytogenetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 Contributed by Peter C. Nowell, January 3, 1984 ABSTRACT The majority of chromosomal rearrange- have demonstrated translocation from 8q24 to 14q32 and ments observed in Burkitt lymphomas involve a translocation deregulation of transcription of the c-myc oncogene (18, 20). between 8q and 14q, while the remaining minority carry vari- Close proximity between immunoglobulin heavy chain and ant translocations between chromosome 8 and either 2 or 22. c-myc DNA sequences on the 14q+ chromosome are a result We have studied the JI Burkitt lymphoma cell line carrying of the translocation (15-18, 20). In Burkitt lines with the 8;22 the variant 2;8 chromosome translocation using a combination rearrangement, there is evidence for translocation of X se- of high-resolution and molecular cytogenetic techniques. We quences to the 8q+ chromosome (9, 10), resulting in tran- have determined that the chromosome 2 breakpoint of the 2;8 scriptional activation of the c-myc that remains on the in- translocation in these cells is in the distal portion of 2pll.2.
    [Show full text]
  • Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 27:870–1041 https://doi.org/10.1038/s41431-019-0408-3 MEETING ABSTRACTS Abstracts from the 51st European Society of Human Genetics Conference: Electronic Posters © European Society of Human Genetics 2019 June 16–19, 2018, Fiera Milano Congressi, Milan Italy Sponsorship: Publication of this supplement was sponsored by the European Society of Human Genetics. All content was reviewed and approved by the ESHG Scientific Programme Committee, which held full responsibility for the abstract selections. Disclosure Information: In order to help readers form their own judgments of potential bias in published abstracts, authors are asked to declare any competing financial interests. Contributions of up to EUR 10 000.- (Ten thousand Euros, or equivalent value in kind) per year per company are considered "Modest". Contributions above EUR 10 000.- per year are considered "Significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal Genetics then compared this data to de novo cases where research based PO studies were completed (N=57) in NY. E-P01.01 Results: MFSIQ (66.4) for familial deletions was Parent of origin in familial 22q11.2 deletions impacts full statistically lower (p = .01) than for de novo deletions scale intelligence quotient scores (N=399, MFSIQ=76.2). MFSIQ for children with mater- nally inherited deletions (63.7) was statistically lower D. E. McGinn1,2, M. Unolt3,4, T. B. Crowley1, B. S. Emanuel1,5, (p = .03) than for paternally inherited deletions (72.0). As E. H. Zackai1,5, E. Moss1, B. Morrow6, B. Nowakowska7,J. compared with the NY cohort where the MFSIQ for Vermeesch8, A.
    [Show full text]
  • The Cytogenetics of Hematologic Neoplasms 1 5
    The Cytogenetics of Hematologic Neoplasms 1 5 Aurelia Meloni-Ehrig that errors during cell division were the basis for neoplastic Introduction growth was most likely the determining factor that inspired early researchers to take a better look at the genetics of the The knowledge that cancer is a malignant form of uncon- cell itself. Thus, the need to have cell preparations good trolled growth has existed for over a century. Several biologi- enough to be able to understand the mechanism of cell cal, chemical, and physical agents have been implicated in division became of critical importance. cancer causation. However, the mechanisms responsible for About 50 years after Boveri’s chromosome theory, the this uninhibited proliferation, following the initial insult(s), fi rst manuscripts on the chromosome makeup in normal are still object of intense investigation. human cells and in genetic disorders started to appear, fol- The fi rst documented studies of cancer were performed lowed by those describing chromosome changes in neoplas- over a century ago on domestic animals. At that time, the tic cells. A milestone of this investigation occurred in 1960 lack of both theoretical and technological knowledge with the publication of the fi rst article by Nowell and impaired the formulations of conclusions about cancer, other Hungerford on the association of chronic myelogenous leu- than the visible presence of new growth, thus the term neo- kemia with a small size chromosome, known today as the plasm (from the Greek neo = new and plasma = growth). In Philadelphia (Ph) chromosome, to honor the city where it the early 1900s, the fundamental role of chromosomes in was discovered (see also Chap.
    [Show full text]
  • Rapid Molecular Assays to Study Human Centromere Genomics
    Downloaded from genome.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Method Rapid molecular assays to study human centromere genomics Rafael Contreras-Galindo,1 Sabrina Fischer,1,2 Anjan K. Saha,1,3,4 John D. Lundy,1 Patrick W. Cervantes,1 Mohamad Mourad,1 Claire Wang,1 Brian Qian,1 Manhong Dai,5 Fan Meng,5,6 Arul Chinnaiyan,7,8 Gilbert S. Omenn,1,9,10 Mark H. Kaplan,1 and David M. Markovitz1,4,11,12 1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; 2Laboratory of Molecular Virology, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay 11400; 3Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan 48109, USA; 4Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan 48109, USA; 5Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109, USA; 6Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA; 7Michigan Center for Translational Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; 8Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA; 9Department of Human Genetics, 10Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA; 11Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA; 12Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, USA The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of cen- tromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious.
    [Show full text]
  • Molecular‑Cytogenetic Study of De Novo Mosaic Karyotype 45,X/46,X,I(Yq)/46,X,Idic(Yq) in an Azoospermic Male: Case Report and Literature Review
    MOLECULAR MEDICINE REPORTS 16: 3433-3438, 2017 Molecular‑cytogenetic study of de novo mosaic karyotype 45,X/46,X,i(Yq)/46,X,idic(Yq) in an azoospermic male: Case report and literature review YUTING JIANG1, RUIXUE WANG1, LINLIN LI1, LINTAO XUE2, SHU DENG1 and RUIZHI LIU1 1Center for Reproductive Medicine, Center for Prenatal Diagnosis First Hospital, Jilin University, Changchun, Jilin 130021; 2Reproductive Medical and Genetic Center, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 520021, P.R. China Received August 11, 2016; Accepted May 9, 2017 DOI: 10.3892/mmr.2017.6981 Abstract. The present study describes a 36-year-old male carries one centromere and duplication of the short or long with the 45,X/46,X,i(Yq)/46,X,idic(Yq) karyotype, who arm, and the idic(Y) consists of two identical arms that are suffered from azoospermia attributed to maturation arrest of positioned as mirror images to one another, with an axis of the primary spermatocyte. To the best of our knowledge, this symmetry lying between two centromeres (3). The two types rare karyotype has not yet been reported in the literature. The of chromosome are often unstable during cell division. results of detailed molecular-cytogenetic studies of isodicen- Patients with iso(Y) or idic(Y) may develop mosaic tric (idic)Y chromosomes and isochromosome (iso)Y, which karyotypes with variable phenotypes, such as spermatogenic are identified in patient with complex mosaic karyotypes, are failure, sexual infantilism, hypospadias, ambiguous genitalia, presented. The presence of mosaicism of the three cell lines and a normal male phenotype (4).
    [Show full text]
  • Trisomy 8 Mosaicism
    Trisomy 8 Mosaicism rarechromo.org Sources Trisomy 8 Mosaicism Trisomy 8 mosaicism (T8M) is a chromosome disorder caused by and the presence of a complete extra chromosome 8 in some cells of References the body. The remaining cells have the usual number of 46 The information in chromosomes, with two copies of chromosome 8 in each cell. this guide is Occasionally T8M is called Warkany syndrome after Dr Josef drawn partly from Warkany, the American paediatrician who first identified the published medical condition and its cause in the 1960s. Full trisomy 8 – where all cells literature. The have an extra copy of chromosome 8 - is believed to be incompatible first-named with survival, so babies and children in whom an extra chromosome author and 8 is found are believed to be always mosaic (Berry 1978; Chandley publication date 1980; Jordan 1998; Karadima 1998). are given to allow you to look for the Genes and chromosomes abstracts or The human body is made up of trillions of cells. Most of the cells original articles contain a set of around 20,000 different genes; this genetic on the internet in information tells the body how to develop, grow and function. Genes PubMed are carried on structures called chromosomes, which carry the (www.ncbi.nlm. genetic material, or DNA, that makes up our genes. nih.gov/pubmed). If you wish, you Chromosomes usually come in pairs: one chromosome from each can obtain most parent. Of these 46 chromosomes, two are a pair of sex articles from chromosomes: XX (a pair of X chromosomes) in females, and XY Unique.
    [Show full text]
  • Supernumerary Chromosome 8 FTNW
    Supernumerary chromosome 8 rarechromo.org Supernumerary chromosome 8 Supernumerary chromosome 8 means that there is a tiny extra part of a chromosome in all or some of the cells of the body. In addition to the 46 chromosomes that everyone has, people with a supernumerary chromosome 8 have a small extra chromosome made from chromosome 8 material. The small extra chromosome can have different possible shapes. It can also have different names. The most common names are: small supernumerary marker chromosome (sSMC ) supernumerary ring chromosome (SRC ), if it’s in the form of a ring Other names you might find in the medical literature include: small accessory chromosome (SAC ) extra structurally abnormal chromosome (ESAC ). Genes and chromosomes Our bodies are made up of billions of cells. Most of the cells contain a complete set of tens of thousands of genes which act like a set of instructions, controlling our growth and development and how our bodies work. Genes are carried on microscopically small, thread-like structures called chromosomes. There are usually 46 chromosomes, 23 inherited from our mother and 23 inherited from our father, so we have two sets of 23 chromosomes in ‘pairs’. Apart from two sex chromosomes (two Xs for a girl and an X and a Y for a boy) the chromosomes are numbered 1 to 22, generally from largest to smallest. Sources & references The information in this leaflet is drawn partly from published medical research where there are reports of around 40 cases. The first-named author and publication date are given to allow you to look for the abstracts or original articles on the internet in PubMed (at www.ncbi.nlm/ nih.gov/pubmed ).
    [Show full text]