Publications by authors named "Arthur Van Damme"
Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.
Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.
Unlabelled: Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.
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- The study aims to improve the diagnosis of Mismatch Repair Deficiency (MMRD), which is important for managing tumors and early detection in individuals with constitutional mismatch repair deficiency (CMMRD).
- Researchers developed a new assay called the Low-pass Genomic Instability Characterization (LOGIC) to detect MMRD and compared its performance with existing diagnostic methods.
- LOGIC demonstrated 100% sensitivity and specificity in detecting MMRD in childhood cancers, outperforming other tests and showing potential for better cancer management and tailored surveillance for patients with CMMRD.
Article Synopsis
- * A study involving 45 tumors from 38 patients indicated that immune checkpoint inhibitors (ICIs) can lead to improved survival rates, especially in tumors with ultra-high mutation rates or specific genetic characteristics.
- * The research highlights the importance of mutation burden and microsatellite instability (MS-indels) in predicting ICI treatment responses, showing that even tumors typically classified as non-responsive can benefit from this type of immunotherapy.
Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.
Patients And Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium.
Article Synopsis
- Replication repair deficiency, resulting from mismatch repair deficiency (MMRD) and/or loss of DNA polymerase proofreading, leads to hypermutation in cancer, with microsatellite instability (MSI) being a key indicator of MMRD.
- Genome-wide analysis reveals a connection between loss of polymerase proofreading and MSI, particularly when both replication repair mechanisms are compromised, highlighting distinct mutation signatures (MS-sigs).
- The study emphasizes the clinical utility of MS-sigs in identifying replication repair deficiencies in cancer patients and predicting their responses to immunotherapy, enhancing diagnosis and treatment strategies.
Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays.
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