Anticipation in lynch syndrome: where we are where we go.
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TLDR
The clinical and molecular features of Lynch syndrome are summarized, with a particular focus on the latest studies that have investigated the molecular mechanisms of genetic anticipation.Abstract:
Lynch syndrome (LS) is the most common form of inherited predisposition to develop cancer mainly in the colon and endometrium but also in other organ sites. Germline mutations in DNA mismatch repair (MMR) gene cause the transmission of the syndrome in an autosomal dominant manner. The management of LS patients is complicated by the large variation in age at cancer diagnosis which requires these patients to be enrolled in surveillance protocol starting as early as in their second decade of life. Several environmental and genetic factors have been proposed to explain this phenotypic heterogeneity, but the molecular mechanisms remain unknown. Although the presence of genetic anticipation in Lynch syndrome has been suspected since 15 years, only recently the phenomenon has been increasingly reported to be present in different cancer genetic syndromes including LS. While the biological basis of earlier cancer onset in successive generations remains poorly known, recent findings point to telomere dynamics as a mechanism significantly contributing to genetic anticipation in Lynch syndrome and in other familial cancers. In this review, we summarize the clinical and molecular features of Lynch syndrome, with a particular focus on the latest studies that have investigated the molecular mechanisms of genetic anticipation.read more
Citations
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Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li–Fraumeni cancer predisposition syndrome
Hany Ariffin,Pierre Hainaut,Anna M. Puzio-Kuter,Soo Sin Choong,Adelyne S. L. Chan,Denis Tolkunov,Gunaretnam Rajagopal,Wenfeng Kang,Leon Li Wen Lim,Shekhar Krishnan,Kok-Siong Chen,Maria Isabel Achatz,Mawar Karsa,Jannah Shamsani,Arnold J. Levine,Chang S. Chan +15 more
TL;DR: No evidence of increased rates of CNVs is found in two successive generations of TP53 mutation carriers and in successive Generations of Trp53-deficient mice, and in multigeneration families, cancer onset was delayed in older compared with recent generations, supporting an alternative model for apparent anticipation.
Journal ArticleDOI
Ovarian Cancer: In Search of Better Marker Systems Based on DNA Repair Defects
TL;DR: Ovarian cancer is the fifth most common female cancer in the Western world, and the deadliest gynecological malignancy, and there is a significant clinical need for reliable and accurate detection methods for ovarian cancer, especially for patients at high risk.
Journal ArticleDOI
Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC).
Mei Hua Wong,Chuen Seng Tan,Soo-Chin Lee,Yvonne Fong Ling Yong,Aikseng Ooi,Joanne Ngeow,Min-Han Tan +6 more
TL;DR: Preliminary evidence of genetic anticipation of RCC in HLRCC syndrome is reported, which may have practical implications on counseling and timing of surveillance initiation and exploration of the underlying mechanisms of anticipation would be of considerable biological interest.
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Toward a Molecular Classification of Colorectal Cancer: The Role of Telomere Length
Esha Baichoo,Lisa A. Boardman +1 more
TL;DR: This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed inTelomere measurement, and concludes with arguments in favor of including telomeres assessment in the molecular profiling of CRCs.
Journal ArticleDOI
Lynch syndrome: a pediatric perspective.
TL;DR: The DNA MMR system, the present understanding of LS in the pediatric population, and the newly identified biallelic form of the disease known as constitutional mismatch repair deficiency syndrome are reviewed.
References
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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.
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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.
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New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC.
TL;DR: The establishment of a set of selection criteria for families with hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) to provide a basis for uniformity in collaborative studies and a definition of HNPCC was proposed that was aimed at helping clinicians to identify families.
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The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC).
TL;DR: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) H. Vasen, M. Mecklin, P. Lynch, and H. Meera Khan present a meta-analysis of 125 cases of patients with central giant cell carcinoma of the colon and rectum found to have had atypical EMTs.
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.