Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘Care for CMMRD’ (C4CMMRD)
Katharina Wimmer,Christian P. Kratz,Hans F. A. Vasen,Olivier Caron,Chrystelle Colas,Chrystelle Colas,Natacha Entz-Werle,Anne-Marie Gerdes,Yael Goldberg,Denisa Ilencikova,Martine Muleris,Martine Muleris,Alex Duval,Alex Duval,Noémie Lavoine,Clara Ruiz-Ponte,Irene Slavc,Brigit Burkhardt,Laurence Brugières +18 more
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TLDR
It is expected that application of the suggested strategy for CMMRD diagnosis will increase the number of patients being identified at the time when they develop their first tumour, allowing adjustment of the treatment modalities, offering surveillance strategies for second malignancies and appropriate counselling of the entire family.Abstract:
Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain and intestinal tract tumours. Patients show a variety of non-malignant features that are indicative of CMMRD. However, currently no criteria that should entail diagnostic evaluation of CMMRD exist. We present a three-point scoring system for the suspected diagnosis CMMRD in a paediatric/young adult cancer patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points. They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches a minimum of three points by adding the points of the malignancy and the additional features. The diagnostic steps to confirm or refute the suspected diagnosis are outlined. We expect that application of the suggested strategy for CMMRD diagnosis will increase the number of patients being identified at the time when they develop their first tumour. This will allow adjustment of the treatment modalities, offering surveillance strategies for second malignancies and appropriate counselling of the entire family.read more
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Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency
Eric Bouffet,Valérie Larouche,Brittany Campbell,Daniele Merico,Richard de Borja,Melyssa Aronson,Carol Durno,Joerg Krueger,Vanja Cabric,Vijay Ramaswamy,Nataliya Zhukova,Gary Mason,Roula Farah,Samina Afzal,Michal Yalon,Gideon Rechavi,Vanan Magimairajan,Michael Walsh,Shlomi Constantini,Rina Dvir,Ronit Elhasid,Alyssa Reddy,Michael Osborn,Michael J. Sullivan,Jordan R. Hansford,Andrew Dodgshun,Nancy Klauber-DeMore,Lindsay L. Peterson,Sunil J. Patel,Scott Lindhorst,Jeffrey Atkinson,Zane Cohen,Rachel Laframboise,Peter B. Dirks,Michael D. Taylor,David Malkin,Steffen Albrecht,Roy W. R. Dudley,Nada Jabado,Cynthia Hawkins,Adam Shlien,Uri Tabori +41 more
TL;DR: This report of initial and durable responses of recurrent GBM to immune checkpoint inhibition may have implications for GBM in general and other hypermutant cancers arising from primary (genetic predisposition) or secondary MMRD.
Journal ArticleDOI
Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer
Alicia Latham,Preethi Srinivasan,Yelena Kemel,Jinru Shia,Chaitanya Bandlamudi,Diana Mandelker,Sumit Middha,Jaclyn F. Hechtman,Ahmet Zehir,Marianne Dubard-Gault,Christina Tran,Carolyn Stewart,Margaret Sheehan,Alexander V Penson,Deborah DeLair,Rona Yaeger,Rona Yaeger,Joseph Vijai,Semanti Mukherjee,Jesse Galle,Mark A. Dickson,Mark A. Dickson,Yelena Y. Janjigian,Yelena Y. Janjigian,Eileen M. O'Reilly,Eileen M. O'Reilly,Neil H. Segal,Neil H. Segal,Leonard B. Saltz,Leonard B. Saltz,Diane Reidy-Lagunes,Diane Reidy-Lagunes,Anna M. Varghese,Anna M. Varghese,Dean F. Bajorin,Dean F. Bajorin,Maria I. Carlo,Maria I. Carlo,Karen Cadoo,Karen Cadoo,Michael Walsh,Michael Walsh,Martin R. Weiser,Martin R. Weiser,Julio Garcia Aguilar,Julio Garcia Aguilar,David S. Klimstra,Luis A. Diaz,Luis A. Diaz,José Baselga,José Baselga,Liying Zhang,Marc Ladanyi,David M. Hyman,David M. Hyman,David B. Solit,David B. Solit,Mark E. Robson,Mark E. Robson,Barry S. Taylor,Kenneth Offit,Michael F. Berger,Michael F. Berger,Zsofia K. Stadler,Zsofia K. Stadler +64 more
TL;DR: MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated, and given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H-D tumor, regardless of cancer type or family cancer history.
Journal ArticleDOI
Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers.
Adam Shlien,Brittany Campbell,Richard de Borja,Ludmil B. Alexandrov,Daniele Merico,David C. Wedge,Peter Van Loo,Patrick S. Tarpey,Paul Coupland,Sam Behjati,Aaron Pollett,Tatiana Lipman,Abolfazl Heidari,Shriya Deshmukh,Na'ama Avitzur,Bettina Meier,Moritz Gerstung,Ye Hong,Diana M. Merino,Manasa Ramakrishna,Marc Remke,Roland Arnold,Gagan B. Panigrahi,Neha P. Thakkar,Karl P. Hodel,Erin E. Henninger,A. Yasemin Göksenin,Doua Bakry,George S. Charames,Harriet Druker,Jordan Lerner-Ellis,Matthew Mistry,Rina Dvir,Ronald Grant,Ronit Elhasid,Roula Farah,Glenn Taylor,Paul C. Nathan,Sarah Alexander,Shay Ben-Shachar,Simon C. Ling,Steven Gallinger,Shlomi Constantini,Peter B. Dirks,Annie Huang,Stephen W. Scherer,Richard Grundy,Carol Durno,Melyssa Aronson,Anton Gartner,M. Stephen Meyn,Michael D. Taylor,Zachary F. Pursell,Christopher E. Pearson,David Malkin,P. Andrew Futreal,Michael R. Stratton,Eric Bouffet,Cynthia Hawkins,Peter J. Campbell,Uri Tabori +60 more
TL;DR: A new mechanism of cancer progression is suggested in which mutations develop in a rapid burst after ablation of replication repair, which implies a threshold compatible with cancer-cell survival.
Journal ArticleDOI
Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead
Veronique Minard-Colin,Laurence Brugières,Alfred Reiter,Mitchell S. Cairo,Thomas G. Gross,Wilhelm Woessmann,Birgit Burkhardt,John T. Sandlund,Denise Williams,Marta Pillon,Keizo Horibe,Anne Auperin,Marie-Cécile Le Deley,Martin Zimmerman,Sherrie L. Perkins,Martine Raphael,Laurence Lamant,Wolfram Klapper,Lara Mussolin,Hélène Poirel,Elizabeth Macintyre,Christine Damm-Welk,Angelo Rosolen,Catherine Patte +23 more
TL;DR: Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse.
Journal ArticleDOI
Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk
Sanne W. ten Broeke,Richard M. Brohet,Carli M. J. Tops,Heleen M. van der Klift,Mary E. Velthuizen,Inge Bernstein,Gabriel Capellá Munar,Encarna B. Gomez Garcia,Nicoline Hoogerbrugge,Tom G.W. Letteboer,Fred H. Menko,Annika Lindblom,Arjen R. Mensenkamp,Pål Møller,Theo A. M. van Os,Nils Rahner,B. Redeker,Rolf H. Sijmons,Liesbeth Spruijt,Manon Suerink,Yvonne J. Vos,Anja Wagner,Frederik J. Hes,Hans F. A. Vasen,Maartje Nielsen,Juul T. Wijnen +25 more
TL;DR: Risks of colorectal cancer and endometrial cancer were found to be markedly lower than those previously reported for the other MMR, and it should be noted that a substantial variation in cancer phenotype within and between families is observed, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.
References
More filters
Journal Article
A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer
C. Richard Boland,Stephen N. Thibodeau,Stanley R. Hamilton,David Sidransky,James R. Eshleman,Randall W. Burt,Stephen J. Meltzer,Miguel A. Rodriguez-Bigas,Riccardo Fodde,G. Nadia Ranzani,Sudhir Srivastava +10 more
TL;DR: The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms.
Journal ArticleDOI
Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability
Asad Umar,C. Richard Boland,Jonathan P. Terdiman,Sapna Syngal,Albert de la Chapelle,Josef Rüschoff,Richard Fishel,Noralane M. Lindor,Lawrence J. Burgart,Richard Hamelin,Stanley R. Hamilton,Robert A. Hiatt,Jeremy R. Jass,Annika Lindblom,Henry T. Lynch,Päivi Peltomäki,Scott D. Ramsey,Miguel A. Rodriguez-Bigas,Hans F. A. Vasen,Ernest T. Hawk,J. Carl Barrett,Andrew N. Freedman,Sudhir Srivastava +22 more
TL;DR: This commentary summarizes the Workshop presentations on HNPCC and MSI testing; presents the issues relating to the performance, specificity, and specificity of the Bethesda Guidelines; outlines the revised Bethesda Guidelines for identifying individuals at risk for H NPCC; and recommend criteria for MSI testing.
Journal ArticleDOI
Clues to the pathogenesis of familial colorectal cancer
Lauri A. Aaltonen,Päivi Peltomäki,Fredrick S. Leach,Pertti Sistonen,Lea Pylkkänen,Jukka-Pekka Mecklin,Heikki Järvinen,Steven M. Powell,Jin Jen,Stanley R. Hamilton,Gloria M. Petersen,Kenneth W. Kinzler,Bert Vogelstein,Albert de la Chapelle +13 more
TL;DR: Molecular features of "familial" cancers were compared with those of sporadic colon cancers, and a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes is suggested.
Journal ArticleDOI
Hereditary Colorectal Cancer
TL;DR: This article provides an in-depth review of the two most common forms of familial colorectal cancer, and the identification of those at risk and the use of appropriate colonoscopic screening.
Journal ArticleDOI
The Molecular Basis of Turcot's Syndrome
Stanley R. Hamilton,Bo Liu,Ramon Parsons,Nickolas Papadopoulos,Jin Jen,Steven M. Powell,Anne J. Krush,Theresa Berk,Zane Cohen,Bernard Têtu,Peter C. Burger,Patricia A. Wood,Fowzia Taqi,Susan V. Booker,Gloria M. Petersen,G. Johan A. Offerhaus,Anne C. Tersmette,Francis M. Giardiello,Bert Vogelstein,Kenneth W. Kinzler +19 more
TL;DR: The association between brain tumors and multiple colorectal adenomas can result from two distinct types of germ-line defects: mutation of the APC gene or mutation of a mismatch-repair gene.
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