Noureddine Boukhatem - Constitutional Oncogenetics

8 Appendix: Summary of the Book

9 ReferencesBirt–Hogg–Dubé syndrome Breast-ovarian cancer syndrome Endocrine neoplasia Familial adenomatous polyposis Familial malignant melanoma Gorlin syndrome Hereditary pheochromocytoma and paraganglioma Infracentesimal syndromes Lynch syndrome Neurofibromatosis RASopathies

10 Index

11 End User License Agreement

1 Introduction Table I.1 Statistics on index patients and their relatives carrying a genetic al... Table I.2 Order of syndromes according to their frequency (as deduced from stati...

2 Chapter 1 Table 1.1. Spectrum of cancers in carriers of BRCA1 and BRCA2 pathogenic variant...

3 Chapter 2Table 2.1. Subtypes of Lynch syndrome (AD: autosomal dominant; AR: autosomal rec...Table 2.2. Estimated lifetime cancer risks in Lynch syndrome by geneTable 2.3. Cumulative incidence of cancer in 75 year old patients with Lynch syn...Table 2.4. Histological characteristics of tumors in relation to Lynch syndrome

4 Chapter 4Table 4.1. Summary of different types of polyposis adenomatous syndromesTable 4.2. MUTYH founder mutations in patients of different ethnic backgrounds; ...

5 Chapter 5Table 5.1. Patient monitoring for MEN1 mutation carriers

6 Chapter 6Table 6.1. Characteristics of hereditary diseases associated with pheochromocyto...Table 6.2. Monitoring program. FPM: free plasma metanephrines; RBC: red blood ce...

7 Chapter 7Table 7.1. Frequency of renal mass type in the general population and in patient...

8 Chapter 8Table 8.1 Clinical classification of different types of RASopathies

9 Chapter 9Table 9.1. Assessment tool for genetic testing (in the context of suspicions of ...

10 Chapter 10Table 10.1. Diagnostic criteria for Gorlin syndrome

1 Introduction Figure I.1. Global path of the index patient and their family members in the onc...

2 Chapter 1 Figure 1.1. Familial pancreatic cancer in a syndromic context; identification of... Figure 1.2. BRCA2 mutations are associated with breast and ovarian cancer, but a... Figure 1.3. Incomplete penetrance. Individual II3 is an obligatory carrier of th... Figure 1.4. Identifying at-risk individuals in the family (by testing family mem... Figure 1.5. Fanconi disease: autosomal recessive transmission. Both parents are ...

3 Chapter 2Figure 2.1. Autosomal dominant transmission Lynch syndrome (MMR +/–): (a) involv...Figure 2.2. CMMRD syndrome (constitutional MMR deficiency) recessive autosomic t...Figure 2.3. Virtual colonoscopy can create a three-dimensional (3D) anatomical m...Figure 2.4. Bladder cancer. Computed tomography (CT) scan of the bladder showing...

4 Chapter 3Figure 3.1. De novo mutations are more or less frequent according to the genes i...Figure 3.2. Family tree showing index case c2 (black arrow) diagnosed with invas...Figure 3.3. Astrocytomas. For a color version of this figure, see www.iste.co.uk...

5 Chapter 4Figure 4.1. (a) Countless polyps are present throughout the colon and rectum, ra...Figure 4.2. Classification of colorectal cancer predisposition syndromes

6 Chapter 5Figure 5.1. MEN1 pedigree; d.: death; dx: age at diagnosis

7 Chapter 6Figure 6.1. Adrenal pheochromocytoma: (a) computed tomography (CT) scan of an ad...Figure 6.2. History of publications linking methylation defects to cancer

8 Chapter 7Figure 7.1. BHD renal tumors, bilateral. Axial view of the mid-section of an ind...

9 Chapter 9Figure 9.1. Beauty spotsFigure 9.2. MelanomasFigure 9.3. Pancreatic cancer in the context of family aggregationFigure 9.4. Metastatic melanoma: (a) computed tomography (CT) scan of the rib, s...

10 Chapter 10Figure 10.1. Photograph of basal cell carcinoma

11 Chapter 17Figure 17.1. VHL, hemangioblastoma. For a color version of this figure, see www....Figure 17.2. VHL, renal tumors, bilateral. For a color version of this figure, s...

12 Chapter 19Figure 19.1. HLRCC, renal tumor. For a color version of this figure, see www.ist...

1 Cover

2 Table of Contents

3 Dedication

4 Title Page SCIENCES Health and Society , Field Director – Bruno Salgues Health Changes and Resistances , Subject Head – Bruno Salgues

5 Copyright First published 2021 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc. Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address: ISTE Ltd 27-37 St George’s Road London SW19 4EU UK www.iste.co.uk John Wiley & Sons, Inc. 111 River Street Hoboken, NJ 07030 USA www.wiley.com © ISTE Ltd 2021 The rights of Noureddine Boukhatem to be identified as the author of this work have been asserted by him in accordance with the Copyright, Designs and Patents Act 1988. Library of Congress Control Number: 2020946632 British Library Cataloguing-in-Publication Data A CIP record for this book is available from the British Library ISBN 978-1-78945-016-3 ERC code: LS2 Genetics, ‘Omics’, Bioinformatics and Systems Biology LS2_5 Epigenetics and gene regulation LS7 Applied Medical Technologies, Diagnostics, Therapies and Public Health LS7_2 Genetic tools for medical diagnosis

6 Foreword Foreword I know Professor Noureddine Boukhatem from Mohamed I University in Morocco well, and I have been able to appreciate during his visits, since 2017, to my oncogenetics department at the Centre Jean-Perrin in Clermont-Ferrand his human qualities, his commitment and his enthusiasm for oncogenetics. A “Tour de France” of major oncogenetic consultations has enabled him to have an informed and multidisciplinary view of modern oncogenetics. Oncogenetics is defined as the management of families presenting a suspected hereditary risk of cancer, which is considered to be the cancer risk factor with by far the highest predictive value. The discovery of the first hereditary cancer risk genes in the late 1980s (TP53 and RB1 genes) provided doctors with a diagnostic tool that was essential to the practice of oncogenetics. The high predictive value of these genetic tests enables the physician to implement screening measures for individuals and families at high risk of cancer in order to improve the prognosis when cancer occurs, but also to implement preventive measures for high-risk cancers whenever possible in order to reduce their incidence. Oncogenetics came into existence about 30 years ago in a few countries, including France, which in 1991 created the Génétique et Cancer (Genetics and Cancer) group, which structured the national organization of oncogenetics through the implementation of the first consultations in Clermont-Ferrand, then in Lyon and then in Paris. It was not until 2002–2003 that the first cancer plan led to the creation of the Institut national du cancer (French National Cancer Institute), which then officially supported oncogenetic activities, first in the molecular diagnosis laboratory, then in consultation and then in the monitoring of people at high risk of cancer. From this support, a territorial network was set up to provide effective care for families at high risk of cancer. France has thus become a model of organization at the national level of oncogenetics. Oncogenetics has developed mainly in Europe and North America. Unfortunately, this discipline remains elementary or reserved for a fortuitous and educated elite in many countries, particularly in Asia and Africa. This is why Professor Noureddine Boukhatem’s approach to writing a book on oncogenetics is valuable and useful for the medical community. He has produced an encyclopedic work with a concise presentation and an extensive bibliography, highly useful as a reference. This work is thus strongly recommended for oncogenetic doctors or students who are going to practice medical genetics. Yves-Jean BIGNON Director of the oncogenetics department Centre Jean-Perrin in Clermont-Ferrand October 2020