Molecular Tumor Board of the University Medical Center Groningen (UMCG-MTB): outcome of patients with rare or complex mutational profiles receiving MTB-advised targeted therapy.

Purpose: Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning.

Differences in the Prognostic Role of Age, Extent of Resection, and Tumor Grade between Astrocytoma IDHmt and Oligodendroglioma: A Single-Center Cohort Study.

Purpose: IDH-mutant glioma is classified as oligodendroglioma or astrocytoma based on 1p19q-codeletion. Whether prognostic factors are similar between these tumor types is not well understood.

Experimental Design: Retrospective cohort study.

Diffuse infiltrating tumour with the molecular profile of an atypical teratoid rhabdoid tumour (AT/RT SHH-1B) in an adult patient.

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.

Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice.

Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples.

Clinical Utility of Circulating Tumor DNA in Patients With Advanced KRAS-Mutated NSCLC Treated With Sotorasib.

Introduction: For patients with KRAS-mutated NSCLC who are treated with sotorasib, there is a lack of biomarkers to guide treatment decisions. We therefore investigated the clinical utility of pretreatment and on-treatment circulating tumor DNA (ctDNA) and treatment-emergent alterations on disease progression.

Methods: Patients with KRAS-mutated NSCLC treated with sotorasib were prospectively enrolled in our biomarker study (NCT05221372).

External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

Background: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands).

Next generation sequencing of high-grade adult-type diffuse glioma in the Netherlands: interlaboratory variation in the primary diagnostic and recurrent setting.

Purpose: Next generation sequencing (NGS) is an important tool used in clinical practice to obtain the required molecular information for accurate diagnostics of high-grade adult-type diffuse glioma (HGG). Since individual centers use either in-house produced or standardized panels, interlaboratory variation could play a role in the practice of HGG diagnosis and treatment. This study aimed to investigate the current practice in NGS application for both primary and recurrent HGG.

Recommendations on scuba diving in Birt-Hogg-Dubé syndrome.

Introduction: Although very uncommon, severe injury and death can occur during scuba diving. One of the main causes of scuba diving fatalities is pulmonary barotrauma due to significant changes in ambient pressure. Pathology of the lung parenchyma, such as cystic lesions, might increase the risk of pulmonary barotrauma.

Liquid Biopsies for Colorectal Cancer and Advanced Adenoma Screening and Surveillance: What to Measure?

Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test.

ATRX Loss in the Development and Prognosis of Conjunctival Melanoma.

Metastatic disease is linked to promoter mutations in conjunctival melanomas (CM). Both promoter and mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions.

Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies.

Background: Peritoneal mesothelioma (PeM) is a rare malignancy with a poor prognosis. Currently there is a lack of effective systemic therapies. Due to the rarity of PeM, it is challenging to study new treatment options.

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol.

Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients.

Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database.

Unexpected moves: a conformational change in MutSα enables high-affinity DNA mismatch binding.

The DNA mismatch repair protein MutSα recognizes wrongly incorporated DNA bases and initiates their correction during DNA replication. Dysfunctions in mismatch repair lead to a predisposition to cancer. Here, we study the homozygous mutation V63E in MSH2 that was found in the germline of a patient with suspected constitutional mismatch repair deficiency syndrome who developed colorectal cancer before the age of 30.

Prevalence, clinical and molecular characteristics of early stage EGFR-mutated lung cancer in a real-life West-European cohort: Implications for adjuvant therapy.

Objectives: The landmark ADAURA study recently demonstrated a significant disease-free survival benefit of adjuvant osimertinib in patients with resected EGFR-mutated lung adenocarcinoma. However, data on prevalence rates and stage distribution of EGFR mutations in non-small cell lung cancer in Western populations are limited since upfront EGFR testing in early stage lung adenocarcinoma is not common practice. Here, we present a unique, real-world, unselected cohort of lung adenocarcinoma to aid in providing a rationale for routine testing of early stage lung cancers for EGFR mutations in the West-European population.

Unexplained mismatch repair deficiency: Case closed.

To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics, MMR deficiency (MMRd) sometimes remains unexplained (UMMRd). Recently, the importance of complete LS diagnostics to explain UMMRd, involving MMR methylation, germline, and somatic analyses, was stressed.