Gerrit A Meijer

Gerrit A Meijer
Netherlands Cancer Institute · Department of Pathology

MD, PhD

About

767
Publications
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24,343
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Publications

Publications (767)
Article
Full-text available
Gain of chromosome arm 13q is one of the most prevalent DNA copy number alterations associated with colorectal adenoma-to-carcinoma progression. The oncogenic miR-17-92 cluster, located at 13q, was found to be overexpressed in colorectal cancer and in adenomas harboring 13q gain. However, to what extent overexpression of this group of microRNAs act...
Article
Full-text available
Introduction The risk of developing gastric cancer is increased in patients treated with radiotherapy for Hodgkin lymphoma (HL) or testicular cancer (TC). This study aims to assess if gastric adenocarcinoma after treatment for HL/TC (t-GC) is molecularly different from gastric adenocarcinoma in the general population. Methods Patients were diagnos...
Article
Purpose: Durable clinical benefit to PD-1 blockade in NSCLC is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCL...
Article
Full-text available
Secretory leukocyte protease inhibitor (SLPI) is a pleiotropic protein produced by healthy intestinal epithelial cells. SLPI regulates NF-κB activation, inhibits neutrophil proteases and has broad antimicrobial activity. Recently, increased SLPI expression was found in various types of carcinomas and was suggested to increase their metastatic poten...
Article
The current increase in number and diversity of targeted anti‐cancer agents poses challenges to the logistics and timeliness of molecular diagnostics (MolDx), resulting in underdiagnosis and treatment. Whole genome sequencing (WGS) may provide a sustainable solution for addressing current as well as future diagnostic challenges. The present study t...
Article
Introduction: Stage III colon cancer patients are offered surgery followed by adjuvant chemotherapy (ACT) according to Dutch clinical guidelines. However, only 15-20% of the patients benefit from ACT: 50% would be cured by surgery alone and are thus being overtreated, while 30-35% will experience a recurrence despite adjuvant treatment. Therefore,...
Article
Introduction: Measurement of tumor-derived DNA molecules in the plasma (ctDNA) has become a useful tool to determine the overall tumor burden in patients with cancer. The ctDNA burden may change over time, decreasing after treatment response and increasing with development of resistance to therapy. Monitoring the dynamics of ctDNA burden over the c...
Article
Background: Genomic instability is a common feature of colorectal cancer (CRC). More than 80% of CRCs exhibit chromosomal instability (CIN) and 15-20% microsatellite instability (MSI). MSI results in a high ‘tumor mutational burden’ (TMB) and is associated with relatively good prognosis in localized CRC. However, for the large group of CIN CRC pati...
Article
Introduction: The distribution of KRAS mutation variants across tumor types is not uniform. The KRAS A146 mutation is predominantly seen in colorectal cancer (CRC) patients. Here, we evaluated how clinical features like tumor load and overall survival differ between metastatic CRC (mCRC) patients carrying distinct somatic KRAS G12, G13, Q61, K117 o...
Article
Interpreting genomic variants in tumor samples presents a challenge in research and the clinical setting. A major barrier is that information about variants is fragmented across disparate databases, and aggregating information from these requires building extensive infrastructure. To this end, we have developed Genome Nexus, a one stop shop for var...
Article
Background To improve colorectal cancer (CRC) survival and lower incidence rates, colonoscopy and/or fecal immunochemical tests (FIT) screening is widely implemented. Although candidate DNA methylation biomarkers have been published to improve or complement FIT, clinical translation is limited. Here, we describe technical and methodological problem...
Article
Background Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal cancer (CRC) compared to patients with IBD only. The aim of this study was to perform an extensive screen of known carcinogenic genomic alterations in patients with PSC-IBD, and to investigate whet...
Article
Aberrantly methylated genes contribute to the landscape of epigenetic alterations in colorectal adenocarcinoma. The global CpG Island methylator phenotype (CIMP) and individually methylated genes are potential prognostic/predictive biomarkers. Research suggests an association between methylated DCR1 (mDCR1) and lack of benefit with irinotecan (IFL)...
Article
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Background: The risk of recurrence after resection of a stage II or III colon cancer, and therefore qualification for adjuvant chemotherapy (ACT), is traditionally based on clinicopathological parameters. However, the parameters used in clinical practice are not able to accurately identify all patients with or without minimal residual disease. Som...
Article
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Around 15–30% of colorectal cancers (CRC) develops from sessile serrated lesions (SSLs). After many years of indolent growth, SSLs can develop dysplasia and rapidly progress into CRC through events that are only partially understood. We studied molecular events at very early stages of progression of SSLs via the MLH1 proficient and deficient pathwa...
Article
PURPOSE Interpretation of genomic variants in tumor samples still presents a challenge in research and the clinical setting. A major issue is that information for variant interpretation is fragmented across disparate databases, and aggregation of information from these requires building extensive infrastructure. To this end, we have developed Genom...
Article
Full-text available
There is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and t...
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With more than 70 different histological sarcoma subtypes, accurate classification can be challenging. Although characteristic genetic events can largely facilitate pathological assessment, large-scale molecular profiling generally is not part of regular diagnostic workflows for sarcoma patients. We hypothesized that whole genome sequencing (WGS) o...
Article
Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case–control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Whole-genome chromosomal copy number changes and mutation status of genes commonly...
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Background Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints. Results We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an...
Article
Full-text available
Purpose Colonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methyl...
Article
Full-text available
PURPOSE Somatic KRAS mutations occur in approximately half of the patients with metastatic colorectal cancer (mCRC). Biologic tumor characteristics differ on the basis of the KRAS mutation variant. KRAS mutations are known to influence patient prognosis and are used as predictive biomarker for treatment decisions. This study examined clinical featu...
Article
Background In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 μg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before an...
Article
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Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection mod...
Article
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Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, p...
Article
Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. Design: Diagnostic test accuracy study. Setting: Colonoscopy-controlled series. Participants: Persons (n = 1284) from...
Conference Paper
p>Background Accurate detection of patients with minimal residual disease (MRD) after resection of localized colon cancer remains an unmet clinical need as these patients might benefit from adjuvant chemotherapy (ACT). For stage II colon cancer, ACT is only indicated in patients with a pT4 tumor without a deficient mismatch repair system (dMMR), ac...
Preprint
Background: Post-colonoscopy colorectal cancers (PCCRCs) pose a challenge in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. Specific features of lesions may contribute for this. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: PCCRCs...
Article
3013 Background: In the next few years numerous drugs will be approved for defined genomic targets, most of these in a tumor agnostic manner. Identifying patients who can benefit from this is critical for the future success of precision medicine, ideally using a single comprehensive test to detect all possible biomarkers. The WIDE study (WGS Implem...
Article
8519 Background: Lung cancer incidence and mortality are increasing worldwide despite more effective treatments. This is primarily due to the late stage of diagnosis when treatments are less effective. Although large randomized trials have demonstrated a significant decrease in lung cancer mortality through screening of high-risk individuals with c...
Article
3531 Background: Population-based screening for colorectal cancer (CRC) aims to decrease incidence and mortality due to precancerous polyp removal, early detection and early treatment of CRC. In the Netherlands, phased introduction of a biennial fecal immunochemical hemoglobin test started in 2014 for individuals aged 55-75. This evaluation of the...
Article
11540 Background: With more than 70 different histological subtypes, accurate classification sarcomas is challenging. Although pathognomonic genetic events aid accurate classification, large-scale molecular profiling is generally not incorporated in regular diagnostic workflows for sarcoma patients. We hypothesized that whole genome sequencing (WGS...
Preprint
Full-text available
Spliced fusion-transcripts are typically identified by RNA-seq without elucidating the causal genomic breakpoints. However, non poly(A)-enriched RNA-seq contains large proportions of intronic reads spanning also genomic breakpoints. Using 1.274 RNA-seq samples, we investigated what additional information is embedded in non poly(A)-enriched RNA-seq...
Article
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Objectives Hodgkin lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia. We evaluated clinicopathological characteristics and risk factors for developing (advanced) neoplasia (AN) in HL survivors. Methods 101 HL survivors (median age 51 years, median age of HL dia...
Article
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Background Bio-Rad droplet-digital PCR is a highly sensitive method that can be used to detect tumor mutations in circulating cell-free DNA (cfDNA) of patients with cancer. Correct interpretation of ddPCR results is important for optimal sensitivity and specificity. Despite its widespread use, no standardized method to interpret ddPCR data is avail...
Article
Introduction Determining prognosis following poor response to neo‐adjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour...
Article
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Background Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillan...
Article
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Aim Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometr...
Article
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Tumor‐derived cell‐free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC‐LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC‐PM). This study evaluated the prese...
Article
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Hodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors (hESCC) by using RNA sequencing and NanoString profiling. Objectives were to investigate differences in RNA signaling between hESCC and sporadic ESCC (sESCC...
Article
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Background ‘Precision oncology’ can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are...
Article
Full-text available
Secretory leukocyte protease inhibitor (SLPI), a pleiotropic protein expressed by healthy intestinal epithelial cells, functions as an inhibitor of NF-κB and neutrophil proteases and exerts antimicrobial activity. We previously showed SLPI suppresses intestinal epithelial chemokine production in response to microbial contact. Increased SLPI express...
Article
Full-text available
Introduction and aim RNF43 is suggested to be involved in the serrated pathway towards colorectal cancer and encodes a transmembrane Ring‐type E3 ubiquitin ligase that negatively regulates the Wnt pathway. This study aims to elucidate the role of RNF43 gene variants in serrated polyposis syndrome (SPS) and serrated polyps. Methods Three cohorts we...
Article
Full-text available
Detection of KRAS, NRAS and BRAF mutations in tumor tissue is currently used to predict resistance to treatment with anti-EGFR antibodies of patients with metastatic colorectal cancer (mCRC). Liquid biopsies are minimally invasive and cell-free circulating tumor DNA (ctDNA) mutation analyses may better represent tumor heterogeneity. This study exam...
Article
Aims: This study aims to investigate the clinicopathological significance of driver mutations in metastatic well-differentiated SI-NETs METHODS AND RESULTS: Whole genome sequencing (WGS) of 35 and next generation sequencing (NGS) of 8 metastatic SI-NETs was performed. Biopsies were obtained between 2015 and 2019. Tumours were classified using the...
Article
Full-text available
AimTo develop a decision model for the population-level evaluation of strategies to improve the selection of stage II colon cancer (CC) patients who benefit from adjuvant chemotherapy.MethodsA Markov cohort model with a one-month cycle length and a lifelong time horizon was developed. Five health states were included; diagnosis, 90-day mortality, d...
Article
Full-text available
Background: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recu...
Conference Paper
Introduction: Stage III colon cancer patients undergo surgery followed by adjuvant chemotherapy (ACT) according to clinical guidelines. However, 50% would be cured by surgery alone and are being overtreated, while 30-35% will relapse despite adjuvant treatment. This means that only 15-20% of the patients benefit from ACT. Therefore, there is a need...
Conference Paper
Introduction: Circulating tumor DNA (ctDNA) from plasma is a promising biomarker. Patients with metastatic colorectal cancer (CRC) often have high ctDNA levels compared to other cancer types. However, it is unclear whether this is also the case for patients with peritoneal metastases from CRC. Aim: To compare the propensity of ctDNA shedding by iso...