Hereditary colorectal cancer & polyposis syndromes
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Mendelian colorectal cancer & polyposis syndromes
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What is Lynch syndrome?
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Mismatch repair machinery
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Current diagnostic route for detection of Lynch syndrome
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Analysis of germline and somatic coding aberrations in MMR genes
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The majority of unexplained dMMR tumours have two somatic MMR mutations
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Individuals with somatic dMMR have a higher age at diagnosis compared to LS patients
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Some individuals with unexplained dMMR ("Lynch-like" syndrome) have clear family histories
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Design of targeted long-read sequencing of MMR genes
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Targeted long-read sequencing allows for the detection of SNV, small indels, exon deletions and Alu insertions
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Targeted long-read MMR gene sequencing of individuals with Lynch-like syndrome
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Non-coding aberrations in MMR genes functionally tested in mini- gene and promoter assays to validate pathogenicity
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What can be the consequence of a deep intronic donor site introduction?
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Functional analysis by use of a mini-gene splice assay
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Noncoding aberrations in MMR genes functionally tested in mini- gene and promoter assays to validate pathogenicity
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Noncoding aberrations in MMR genes functionally tested in mini-gene and promoter assays to validate pathogenicity
21
Summary & Future perspective
Description:
Explore the latest research on Lynch syndrome and mismatch repair genes in this 29-minute webinar presented by Dr. Richarda De Voer, assistant professor at Radboud University Medical Centre. Delve into the genetic predisposition for early-onset colorectal and endometrial cancers, focusing on non-coding aberrations in mismatch repair genes. Learn about current diagnostic techniques, the role of somatic mutations, and the application of targeted long-read sequencing in identifying unexplained cases. Gain insights into functional testing methods for validating pathogenicity of non-coding aberrations. Understand the implications of this research for improving Lynch syndrome diagnosis and uncovering the missing heritability in unexplained cases.
Non-Coding Aberrations in Mismatch Repair Genes Underlie a Substantial Part of the Missing Heritability in Lynch Syndrome