Hereditary brain tumor with a homozygous germline mutation in PMS2 : pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome

AbstractPrecise genetic counseling and prenatal diagnosis are often hindered by incomplete penetrance of risk variance and complex patterns of inheritance. Here, we performed a clinical and genetic study of a five-generation Pakistani family with a history of multiple cases of childhood brain tumors. Six affected individuals died of brain tumors at very early ages and three were confirmed as having a homozygous mutation in exon 6 of thePMS2 gene (c.543delT). Fifteen members of the family were identified as heterozygous carriers of this mutation with a lack of cancer incidence. Both clinical manifestations and genetic test results of brain tumor patients in the family support the diagnosis of constitutional mismatch repair deficiency (CMMRD) syndrome, a condition in which individuals carry homozygous germline mutations in mismatch repair machinery genes with an early onset of malignancies such as glioma. This information was used to guide prenatal diagnosis with genetic testing on chorionic villus samples for the family. This is the first report of prenatal genetic diagnosis of hereditary brain tumor.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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CCR Grand Rounds Dr. Jabado ’ s research focuses on elucidating genetic signatures of pediatric astrocytomas and examining how they compare to adults. These are deadly brain tumors that originate in the brain and include glioblastomas (GBM, the highest grade of astrocytomas), which are one of the deadliest cancers in humans. Her group uncovered that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. They also identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mut...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
Parents of Abbie Mifsud created the charity that has funded vital research on brain stem tumoursResearchers say they are close to testing a drug that could tackle a previously untreatable childhood brain cancer. The condition is known as DIPG – diffuse intrinsic pontine glioma – and every year it affects between 30 to 40 boys and girls, aged between five and 10. All develop tumours caused by the condition and die, often within months of their diagnoses.But now scientists believe they may soon be able to tackle the condition – and one of the key organisations involved is a remarkable charity set up by Aman...
Source: Guardian Unlimited Science - Category: Science Authors: Tags: Drugs Health Science Society UK news Source Type: news
Abstract Pediatric brain tumors are the leading cause of childhood cancer-related death. Immunotherapy is a powerful new approach for treating some refractory cancers; applying this 'fourth pillar' of cancer treatment to pediatric brain tumors is an exciting but challenging prospect. This review offers new perspectives on moving towards successful immunotherapy for pediatric brain tumors, focusing on pediatric high-grade glioma (HGG), a subgroup with universally poor outcomes. We cover chimeric antigen receptor T cell (CAR-T) therapy, vaccine therapy, and checkpoint inhibition in this context, and focus on the nee...
Source: Trends in Immunology - Category: Allergy & Immunology Authors: Tags: Trends Immunol Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive paediatric brain tumour with fatal outcome. The Individualised Therapy For Relapsed Malignancies In Childhood (INFORM) registry study offers comprehensive molecular profiling of high-risk tumours to identify target  alterations for potential precision therapy. We analysed molecular characteristics and clinical data after brainstem biopsy of all enrolled newly diagnosed DIPGs.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors. Introduction Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBC...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
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Source: Annual Review of Public Health - Category: International Medicine & Public Health Authors: Tags: Annu Rev Public Health Source Type: research
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