Translocations in solid tumors

209 Pages·2002·1.854 MB·English

by  C S Cooper, Jonathan A Fletcher

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M
EDICAL
I
NTELLIGENCE
U 22
NIT
Translocations
in Solid Tumors
Colin S. Cooper, BSc, PhD, DSc
The Institute of Cancer Research:
Royal Cancer Hospital
Surrey, United Kingdom
Landes Bioscience Eurekah.com
GEORGETOWN, TEXAS AUSTIN, TEXAS
U.S.A. U.S.A.
T S T
RANSLOCATIONS IN OLID UMORS
Medical Intelligence Unit
Eurekah.com
Landes Bioscience
Copyright ©2002 Eurekah.com
All rights reserved.
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Library of Congress Cataloging-in-Publication Data
Cooper, C.S. (Colin S.), 1954—
Translocations in solid tumors/ Colin S. Cooper, Jonathan A. Fletcher.
p.; cm.--(Medical intelligence unit)
Includes bibliographical references and index.
ISBN 1-58706-033-7 (alk. paper)
1. Cancer--Genetic aspects. 2. Translocation (Genetics). I. Fletcher, Jonathan A.
II. Title. III. Series.
[DNLM: 1. Neoplasms--genetics. 2. Translocation (Genetics). QZ 202 C7755t 2000]
RC268.4.C66 2000
616.99'4042--dc21
99-056723
CONTENTS
Preface .................................................................................................x
1. Cytogenetics of Solid Tumors............................................................. 1
Jonathan A. Fletcher
Introduction..........................................................................................1
Background Information.......................................................................2
General Approach .................................................................................2
Molecular Cytogenetics.........................................................................6
Terminology .........................................................................................7
Diagnosis ..............................................................................................7
Prognosis...............................................................................................9
Biologic Insights..................................................................................10
2. Molecular Cytogenetics of Complex Chromosomal Rearrangements 14
R.F. Suijkerbuijk, A. Simons and A. Geurts van Kessel
Introduction........................................................................................14
Fluorescence in Situ Hybridization......................................................15
Multiplex Fish and Spectral Karyotyping.............................................19
Flow Cytometry of Chromosomes.......................................................21
Chromosome Microdissection.............................................................21
Comparative Genomic Hybridization .................................................22
Representational Difference Analysis...................................................25
Epilogue..............................................................................................29
Acknowledgment.................................................................................29
3. Chromosome Translocations in Benign Solid Tumors..................... 40
Wim J.M. Van de Ven, Koen Kas, Marleen M.R. Petit,
Eric F.P.M. Schoenmakers and Marianne L. Voz
Introduction........................................................................................40
Frequent Chromosome Aberrations in Benign Solid Tumors..............41
HMGIC, a Common Genetic Denominator in Benign Solid Tumor
Development...................................................................................43
PLAG1 a Benign Oncogene Frequently Activated in Pleomorphic
Adenomas .......................................................................................48
Perspectives.........................................................................................54
Acknowledgments...............................................................................55
4. Chromosomal Translocations in Alveolar Rhabdomyosarcoma........ 59
Frederic G. Barr
Clinical and Pathologic Features of Alveolar Rhabdomyosarcoma.......59
Cytogenetics of ARMS........................................................................59
Mapping and Cloning of Loci Involved in 2;13 Translocation............60
Paired Box Family of Transcription Factors.........................................61
Fork Head Family of Transcription Factors.........................................63
Chimeric Products Generated by 2;13 Translocation..........................64
Chimeric Products Generated by 1;13 Translocation..........................65
Molecular Diagnostic Evaluation of Chimeric Products......................66
Expression Characteristics of Wild-Type and Chimeric Products........67
DNA Binding Properties of Wild-Type and Chimeric Proteins...........68
Transcriptional Properties of Wild-Type and Chimeric Proteins.........69
Transcriptional Targets of Wild-Type and Chimeric Proteins.............70
Phenotypic Roles of Wild-Type and Chimeric Proteins.......................70
Conclusions.........................................................................................72
5. Chromosome Translocations in the Ewing Family of Tumors......... 77
Olivier Delattre and Nicolas Sévenet
Clinical and Pathological Features of the Ewing Family of Tumors.....77
Genetics of Ewing Tumor...................................................................78
From Genetics to the Clinic................................................................79
Biology of Ewing Tumor.....................................................................81
Future Considerations.........................................................................82
6. The TLS-CHOP Oncoprotein and Human Liposarcoma................. 86
Masahiko Kuroda, John Sok, and David Ron
Introduction........................................................................................86
Current Research.................................................................................86
Acknowledgments ...............................................................................97
7. Synovial Sarcoma............................................................................ 102
Janet M. Shipley and Colin S. Cooper
Introduction......................................................................................102
Pathology and Differential Diagnosis ................................................102
Cytogenetics......................................................................................103
Breakpoint Position on Chromosome X and Gene Cloning..............104
Characterization of the SYT-SSX, SSX and SYT Genes.....................105
Functional Consequences of SYT-SSX Fusion Proteins.....................106
Detecting the t(X;18) and Associated Fusion Gene Products
to Aid Diagnosis............................................................................107
Involvement of the SSX Genes and Correlations
with Clinicopathological Features..................................................108
Future Directions..............................................................................110
Acknowledgments .............................................................................110
8. Chromosome Translocations in Dermatofibrosarcoma................. 114
Claude Turc-Carel
Introduction......................................................................................114
t(17;22)(q22;q13) and Ring Chromosomes are Characteristic
Cytogenetic Features of DP and Gcf .............................................115
The Chromosome Rearrangements Bring Together PDGFB
and COL1A1 Genes ......................................................................115
The Chimeric Sequence Formed by Fusion of the COL1A1
and PDGFB Genes Possesses a Transforming Activity...................116
Acknowledgments .............................................................................117
9. ETV6-NTRK3 Gene Fusions in Spindle Cell Tumors
of Early Childhood ......................................................................... 119
Poul H.B. Sorensen
Introduction......................................................................................119
Differential Diagnosis of Cellular Spindle Cells Tumors in Early
Childhood.....................................................................................119
Cytogenetics of Childhood Cellular Spindle Cells Tumors................120
Identification of a der(15)t(12;15)(p13;q25) in CFS.........................120
Complex Translocations in CFS........................................................121
Disruption of the ETV6 Gene in CFS...............................................121
Human ETV6 and ETV6 Gene Fusions In Human Leukemias.........122
ETV6 is Fused to the 15q25 NTRK3 Neurotrophin-3 Receptor
Gene in CFS .................................................................................122
Structure of the ETV6-NTRK3 Chimeric Protein..............................123
Human NTRK3 and the NTRK Family of Neurotrophin
Receptors.......................................................................................124
ETV6-NTRK3 Transforms NIH3T3 Cells ........................................124
Predicted Function of ETV6-NTRK3................................................125
NTRK3 Signaling Pathways...............................................................125
Unique Aspects of the ETV6-NTRK3 Oncoprotein...........................127
ETV6-NTRK3 Expression as a Diagnostic Marker for CFS...............128
ETV6-NTRK3 Expression in Congenital Mesoblastic Nephroma......129
Summarizing Remarks.......................................................................129
10. Thyroid Cancer............................................................................... 133
Marco A. Pierotti, Italia Bongarzone, Maria Grazia Borrello,
Angela Greco, Silvana Pilotti and Gabriella Sozzi
Introduction......................................................................................133
Follicular Adenomas and Carcinomas................................................134
Papillary Carcinomas.........................................................................134
Anaplastic Carcinomas......................................................................142
Conclusions.......................................................................................142
Acknowledgements............................................................................144
11. Renal Carcinoma ............................................................................ 149
Colin S. Cooper and Janet M. Shipley
Introduction......................................................................................149
Classification.....................................................................................149
Aetiology...........................................................................................150
Molecular Cytogenetic Studies..........................................................151
Fusion of TFE3 to the PSF Splicing Factor Gene..............................157
Fusion of TFE33 to the (NonOp54nrb) Gene......................................157
Possible Mechanisms of Transformation ...........................................159
Methods for Detection of Alterations of the TFE3 Gene...................160
Do Tumors Containing Alterations in TFE3 Represent a Distinct
Class of Papillary Renal Cancer?....................................................160
The Role of the MET Gene in Papillary Renal Carcinoma
Development.................................................................................161
Wilm’s Tumors.................................................................................162
Future Directions..............................................................................163
Acknowledgments .............................................................................163
12. Molecular Diagnostics .................................................................... 167
Marc Ladanyi
Introduction......................................................................................167
EWS Rearrangement Analysis by Southern Blotting..........................167
Ews-Fli1: The Most Variable Gene Fusion........................................169
EWS-ERG: Molecular Diagnostic Distinction from EWS-FLI1.........170
EWS-ATF1........................................................................................171
EWS-WT1.........................................................................................171
EWS-CHN........................................................................................172
SYT-SSX............................................................................................173
Molecular Diagnosis of Solid Tumors in Archival Pathology
Material.........................................................................................174
Conclusion: Molecular Diagnostics and Common Sense...................174
Acknowledgements............................................................................176
13. Toward New Approaches: Targeting Tumor Specific Molecular
Alterations with Immune Based Therapy........................................ 180
Crystal L. Mackall, Theresa J. Goletz, Jay A. Berzofsky
and Lee J. Helman
Evolving Principles of Tumor Immunology ......................................181
Approaches for the Induction of Immune Responses
to Novel Fusion Proteins...............................................................185
Incorporation of Immune Based Therapies as Adjuncts
to Standard Treatment Regimens..................................................188
Conclusion........................................................................................191
Index............................................................................................... 196
EDITORS
Colin S. Cooper, BSc, PhD, DSc
The Institute of Cancer Research
Royal Cancer Hospital
Surrey, United Kingdom
Chapters 7, 11, 12
CONTRIBUTORS
Frederic G. Barr A. Geurts van Kessel
Department of Pathology Department of Human Genetics
and Laboratory Medicine University Hospital
University of Pennsylvania School Nijmegen, The Netherlands
of Medicine Chapter 2
Philadelphia, Pennsylvania, U.S.A.
Chapter 3 Theresa J. Goletz
Pediatric Oncology Branch
Jay A. Berzofsky and Metabolism Branch
Pediatric Oncology Branch Division of Clinical Sciences
and Metabolism Branch National Cancer Institute
Division of Clinical Sciences Bethesda, Maryland, U.S.A.
National Cancer Institute Chapter 13
Bethesda, Maryland, U.S.A.
Chapter 13 Angela Greco
Division of Experimental Oncology
Italia Bongarzone Division of Anatomical and Cytology
Division of Experimental Oncology Istituto Nazionale Tumori
Division of Anatomical and Cytology Milan, Italy
Istituto Nazionale Tumori Chapter 10
Milan, Italy
Chapter 10 Jonathan A. Fletcher
Brigham and Women’s Hospital
Maria Grazia Borrello Children’s Hospital
Division of Experimental Oncology and Massachusetts General Hospital
Division of Anatomical and Cytology Department of Pathology
Istituto Nazionale Tumori Boston, Massachusetts, U.S.A.
Milan, Italy Chapter 1
Chapter 10
Lee J Helman
Olivier Delattre Pediatric Oncology Branch
Institut Curie Section de Recherche and Metabolism Branch
Paris, France Division of Clinical Sciences
Chapter 5 National Cancer Institute
Bethesda, Maryland, U.S.A.
Chapter 13
Koen Kas Silvana Pilotti
Laboratory for Molecular Oncology Division of Experimental Oncology
Center for Human Genetics Division of Anatomical and Cytology
University of Leuven and Flanders Istituto Nazionale Tumori
Interuniversity Milan, Italy
Institute for Biotechnology Chapter 10
Belgium
Chapter 4 David Ron
Department of Medicine
Masahiko Kuroda Skirball Institute of Biomolecular
Department of Pathology Medicine
Faculty of Medicine NYU Medical Center
University of Tokyo New York, New York, U.S.A.
Tokyo, Japan Chapter 6
Chapter 6
Eric F.P.M. Schoenmakers
Marc Ladanyi Laboratory for Molecular Oncology
Departments of Pathology & Human Center for Human Genetics
Genetics University of Leuven and Flanders
Memorial Sloan-Kettering Cancer Center Interuniversity
New York, New York, U.S.A. Institute for Biotechnology
Chapter 12 Belgium
Chapter 4
Crystal L. Mackall
Pediatric Oncology Branch Nicholas Sévenet
and Metabolism Branch Institut Curie Section de Recherche
Division of Clinical Sciences Paris, France
National Cancer Institute Chapter 5
Bethesda, Maryland, U.S.A.
Chapter 13 Janet M. Shipley
Institute of Cancer Research
Marleen M. R. Petit Haddow Laboratories
Laboratory for Molecular Oncology Surrey, U.K.
Center for Human Genetics Chapters 7, 11, 12
University of Leuven and Flanders
Interuniversity A. Simons
Institute for Biotechnology Department of Human Genetics
Belgium University Hospital
Chapter 4 Nijmegen, The Netherlands
Chapter 2
Marco A. Pierotti
Division of Experimental Oncology John Sok
Division of Anatomical and Cytology Department of Pathology
Istituto Nazionale Tumori Faculty of Medicine
Milan, Italy University of Tokyo
Chapter 10 Tokyo, Japan
Chapter 6
Poul H.B. Sorensen Marianne L. Voz
Department of Pathology Laboratory for Molecular Oncology
British Columbia’s Children's Hospital Center for Human Genetics
Vancouver, Canada University of Leuven and Flanders
Chapter 9 Interuniversity
Institute for Biotechnology
Gabriella Sozzi Belgium
Division of Experimental Oncology Chapter 4
Division of Anatomical and Cytology
Istituto Nazionale Tumori Wm. J. M. Van de Ven
Milan, Italy Laboratory for Molecular Oncology
Chapter 10 Center for Human Genetics
University of Leuven & Flanders
Ron F. Suijkerbuijk Interuniversity
Department of Human Genetics Institute for Biotechnology
University Hospital Belgium
Nijmegen, The Netherlands Chapter 4
Chapter 2
Claude Turc-Carel M.D.
Laboratoire de Genetique
Chromosomique des Tumerus
Nice, France
Chapter 8