: Katalin Balogh, Attila Patocs
: Katalin Balogh, Attila Patocs
: SuperMEN1 Pituitary, Parathyroid and Pancreas
: Springer-Verlag
: 9781441916648
: Advances in Experimental Medicine and Biology
: 1
: CHF 87.00
:
: Nichtklinische Fächer
: English
: 136
: Wasserzeichen/DRM
: PC/MAC/eReader/Tablet
: PDF
The vast expansion in research on tumorigenesis has greatly increased our understanding of tumor development in patients with inherited endocrine tumor syndromes. This book provides an up-to-date summaryfrom clinical basics and latest follow-up guidelines to the most recent molecular findings in multiple endocrine neoplasia Type I syndrome. Articles have been assembled by acknowledged experts in their respective fields to provide current perspectives on the clinical and genetic backgroundsofthis syndrome and to review carefully the latest discoveries concerning the possible functions and interactions ofmenin, the protein encoded by the MEN1gene,including itspossible role incell cycle regulation,hematopoiesis,and bone development. The goal ofthe book is also to present the most recent findings and the broadest aspects of the role of menin in tumorigenesis of the endocrine glands involved in MEN I syndrome (pituitary, parathyroid, endocrine pancreas and adrenal). The connection between the basic experimental and clinical points of view are highlighted through a discussion on animal models, which explores the field in both an inspiring and questioning manner with a focus on areas that remain to be clarified. Our goal was to bring together clinicians and basic researchers who represent a wide range of interests in this particular field of endocrine oncology. Presentingacomprehensive and current overviewofbasic experimental and clinical findings, this book can bring us closer to understanding endocrine tumorigenesis in multiple endocrine neoplasia Type I. Katalin Balogh, MD, PhD Attita Patocs, MD, MSc, PhD v ABOUT THEEDITORS. . .

Katalin Balogh, MD, PhD: I graduated from Semmelweis University, Budapest as a Medical Doctor in 2001 and defended my PhD thesis on the clinical and genetic aspects of multiple endocrine neoplasia Type 1 in 2007. Working as a student at the Department of Physiology, then as a physician at the 2nd Department of Medicine, Semmelweis University, Budapest, I always had the inspiration to build bridges between patients, clinicians and researchers. Being a part of connecting different fields of medicine has always been and still remains a challenge for me. My main research interest is endocrine oncology. I am a member of the Endocrine Society and an international scholarship has afforded me the opportunity to work as a research fellow in Toronto. I hope to continue to build connections between people, continents and nations.

Attila Patocs MD, MSc, PhD: I completed my medical and PhD training at Semmelweis University, Budapest, Hungary in 1998 and 2005, respectively. My interest has always focused on experimental laboratory work; therefore I attended and completed a biomedical engineering training at the Budapest Technical University in 2000. Between 2005-2007 I participated in a two-year postdoctoral fellowship in Dr. Charis Eng's laboratory at the Comprehensive Cancer Center of the Ohio State University and at the Genomic Medicine Institute of the Cleveland Clinic. Back in my home country from 2008 I am head of the Central Isotope Diagnostic Laboratory at the Semmelweis University and as a research associate I am working with the Molecular Medicine Research Group of the Hungarian Academy of Sciences. My research focuses on genetic and genomic characterization of endocrine tumors, on understanding of glucocorticoid signaling and on development of new, routine and molecular biological laboratory methods for diagnosis of endocrine disorders.

PREFACE6
ABOUT THEEDITORS...7
ABOUT THE EDITORS...8
PARTICIPANTS9
Table Contents11
ACKNOWLEDGEMENTS14
CHAPTER 1 MENl Clinical Background15
Abstract15
Introduction15
Clinical Features16
Diagnosis of MEN120
MEN1 Variants and Phenocopy20
Diagnostics of MEN1-Related Tumors22
HPT22
Pancreatic Islet Tumors22
Laboratory Diagnosis22
Imaging22
Pituitary Tumors22
Adrenal Tumors23
Carcinoid Tumors23
Nonendocrine Tumors23
Screening for MEN1 Manifestations23
Indications for MEN1 Germline Mutation Screening23
Therapy25
Hyperparathyroidism25
Endocrine Pancreas Tumors25
Pituitary Tumors26
Surveillance26
Comments and Conclusion26
References27
CHAPTER 2 Genetic Background of MEN1: From Genetic Homogeneity to Functional Diversity30
Abstract30
Introduction: The History of a Rare Endocrine Genetic Disease30
On the Nature of the MEN1 Gene31
What Do We Learn from the Hereditary Mutations of the MEN1 Gene?34
Importance of MEN1 in Endocrine Tumorigenesis34
Is MEN1 a Genome Instability Syndrome?35
Conclusion36
Acknowledgements36
References37
CHAPTER 3 Menin: The Protein Behind the MEN1 Syndrome40
Abstract40
Introduction40
Menin Is a Nuclear Protein-Role of the C-Terminal Region40
Leucine-Rich Domains in Menin42
GTPase Signature Motif43
Post-Translational Modification in Response to DNA Damage43
Conservation ofMenin Structure, Protein Interactions and Function43
Conclusion46
Acknowledgements47
References47
CHAPTER 4 Cellular Functions of Menin50
Abstract50
Introduction50
Cell Cycle50
Menin andthe Cell Cycle51
Menin andthe Retinoblastoma Protein51
Menin and CDK Inhibitors51
Menin and GTPases53
Menin and]unD53
Menin and Activator DIS-Phase Kinase (ASK)54
Menin and TGF- ß Family Members54
Cell CycleCheckpoints and DNA Repair56
Menin and Genomic Instability56
Menin, DNA Binding and ATR-CHKl Pathway56
Menin and FANCD258
Menin and RPA258
Menin and FOXN3 (CHES1)58
Chromatin Remodeling58
Menin and Transcriptional Regulation58
Menin and Histone Deacetylase58
Menin and Histone Methyltransferase60
Menin, Chromatin and Gene Expression60
Conclusion60
Acknowledgements60
References61
CHAPTER5 The Role of Menin in Hematopoiesis64
Abstract64
Introduction64
Menin Is Associated with MLL, a Histone Methyltransftrase Rearranged in Leukemia64
Role of Menin in Hematopoiesis66
Role of Menin in Leukemogenesis67
Conclusion68
References69
CHAPTER 6 Role of Menin in Bone Development71
Abstract71
Introduction71
Menin and TGF- ß Signaling71
Menin and AP-1 Signaling72
BMP, TGF- ß and AP-1 Signaling in the Osteoblast72
Role of Menin in Early Stage Osteoblast Differentiation74
Menin and TGF- ß Pathway in Osteoblast Differentiation74
Menin and JunD in the Osteoblast76
Conclusion77
Acknowledgements78
References78
CHAPTER 7 Activin, TGF- ß and Menin in Pituitary Tumorigenesis80
Abstract80
Introduction80
Genetics of Pituitary Adenomas: Role of MEN1 Mutations81
'The Activin/TGF-B Su