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.
Keywords: Anticipation, lynch syndrome, MMR genes, microsatellite instability, telomere length, telomere dynamics, cancer, GWAS, mutations, MSH2 genes
Current Genomics
Title: Anticipation in Lynch Syndrome: Where We Are Where We Go
Volume: 12 Issue: 7
Author(s): Cristina Bozzao, Patrizia Lastella and Alessandro Stella
Affiliation:
Keywords: Anticipation, lynch syndrome, MMR genes, microsatellite instability, telomere length, telomere dynamics, cancer, GWAS, mutations, MSH2 genes
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.
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Cite this article as:
Bozzao Cristina, Lastella Patrizia and Stella Alessandro, Anticipation in Lynch Syndrome: Where We Are Where We Go, Current Genomics 2011; 12 (7) . https://dx.doi.org/10.2174/138920211797904070
DOI https://dx.doi.org/10.2174/138920211797904070 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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