115PEvaluation of microsatellite instability testing through cell-free DNA sequencing

ConclusionsOur evaluation indicates that we can accurately determine MSI status in cfDNA samples with a wide range of tumor content.Legal entity responsible for the studyThe authors.FundingIllumina.DisclosureS. Zhang: Full / Part-time employment: Illumina. J.S. LoCoco: Full / Part-time employment: Illumina. A. Mentzer: Full / Part-time employment: Illumina. B.M. Crain: Full / Part-time employment: Illumina. S. Katz: Full / Part-time employment: Illumina. G. Berry: Full / Part-time employment: Illumina. Y. Fu: Full / Part-time employment: Illumina. T. Jiang: Full / Part-time employment: Illumina. C. Zhao: Full / Part-time employment: Illumina. S. Bilke: Full / Part-time employment: Illumina. T. Pawlowski: Full / Part-time employment: Illumina. K. Kruglyak: Full / Part-time employment: Illumina.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research

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Abstract MMR-deficient colorectal cancers (dMMR CRC) are characterized by the expression of highly-immunogenic neoantigen peptides, which stimulate lymphocytic infiltration as well as up-regulation of inflammatory cytokines. These features are key to understanding why immunotherapy (specifically PD-1 and/or CTLA-4 checkpoint blockade) has proved to be highly effective for the treatment of patients with advanced dMMR CRC. Importantly, pre-clinical studies also suggest that this correlation between potent tumor neoantigens and the immune microenvironment is present in early (pre-malignant) stages of dMMR colorectal ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsThis ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Duraturo F, Liccardo R, De Rosa M, Izzo P Abstract Lynch syndrome (LS) is an autosomal dominant genetic disorder associated with germline mutations in DNA mismatch repair (MMR) genes. The carriers of pathogenic mutations in these genes have an increased risk of developing a colorectal cancer and/or LS-associated cancer. The LS-associated cancer types include carcinomas of the endometrium, small intestine, stomach, pancreas and biliary tract, ovary, brain, upper urinary tract and skin. The criteria for the clinical diagnosis of LS and the procedures of the genetic testing for identification of pathogenetic ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
AbstractLynch syndrome is one of the most common hereditary cancer predisposition syndromes and is associated with increased risks of colorectal and endometrial cancer, as well as multiple other cancer types. While the mechanism of mismatch repair deficiency and microsatellite instability and its role in Lynch-associated carcinogenesis has been known for some time, there have been significant advances recently in diagnostic testing and the understanding of the molecular pathogenesis of Lynch tumors. There is also an increased awareness that the clinical phenotype and cancer risk varies by specific mismatch repair mutation,...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Abstract Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include ML...
Source: Acta Bio-Medica : Atenei Parmensis - Category: General Medicine Authors: Tags: Acta Biomed Source Type: research
This article, an overview of the expanding role of MSI in CRC, covers its clinical significance, the available data on molecular profiling, novel perspectives on MSI testing, biomarkers in MSI-H CRC, immunotherapy resistance, and novel immunotherapy strategies. PMID: 30543589 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
te; T Abstract Lynch syndrome is a genetic condition defined by a germline mutation of an MMR (MisMatch Repair) gene leading to a defective DNA MMR system. Therefore, it is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer (CRC) and endometrial cancer (EC). Lynch syndrome-related CRC accounts for 3% of all CRC. Lynch syndrome also accounts for 2% of all EC. In case of Lynch syndrome, there is usually a familial history of cancer defined by the Amsterdam and Bethesda criteria. Diagnosis is made by tumor testing with (i) MMR immunohistochemistry and (ii) PCR for MSI (microsate...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
CONCLUSION: Advanced endometrial cancer can rarely (~7%) show somatic loss of MMR protein expression in recurrent or metastatic sites compared to matched paired primary tumor. MMR testing of recurrent or metastasis should be considered for guiding immunotherapy if primary uterine tumor exhibits abnormal subclonal MMR loss. PMID: 30340772 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
Abstract Ovarian clear cell carcinoma (OCCC) is distinctive from other histological types of epithelial ovarian cancer, with genetic/epigenetic alterations, a specific immune-related molecular profile, and epidemiologic associations with ethnicity and endometriosis. These findings allow for the exploration of unique and specific treatments for OCCC. Two major mutated genes in OCCC are PIK3CA and ARID1A, which are frequently coexistent with each other. Other genes' alterations also contribute to activation of the PI3K (e.g. PIK3R1 and PTEN) and dysregulation of the chromatin remodeling complex (e.g. ARID1B, and SMA...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
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