Guy Van Camp's research while affiliated with University of Antwerp and other places
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Publications (522)
Purpose Analysis of methylation markers in liquid biopsies is a promising technique for the follow-up of metastatic colorectal cancer (mCRC) patients, since they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monit...
Otosclerosis is one of the most common causes of hearing loss in young adults. It has a prevalence of 0.3–0.4% in the European population. Clinical symptoms usually occur between the second and fifth decade of life. Different studies have been performed to unravel the genetic architecture of the disease. Recently, a genome-wide association study (G...
Background
Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients’ blood gene expression and applying machine learning on the transcriptome data to develop predictive models.
M...
The increase in recent scientific studies on cancer biomarkers has brought great new insights into the field. Moreover, novel technological breakthroughs such as long read sequencing and microarrays have enabled high throughput profiling of many biomarkers, while advances in bioinformatic tools have made the possibility of developing highly reliabl...
Purpose
Microtia describes a spectrum of auricular malformations ranging from mild dysplasia to anotia. A vast majority of microtia patients demonstrate congenital aural atresia (CAA). Isolated microtia has a right ear predominance (58–61%) and is more common in the male sex. Isolated microtia is a multifactorial condition involving genetic and env...
In this study, we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults. We sequenced the coding, 5′-UTR and 3′-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls from six different subpopulations. The association between variants in ACAN and the disease...
Otosclerosis is a relatively common cause of hearing impairment, characterized by abnormal bone remodeling of the middle and inner ear. In about 50–60% of the patients, the disease is present in a familial form. In most of these families, otosclerosis seems to be caused by a small number of genetic factors (oligogenic) while only in a small number...
DNA methylation alterations have already been linked to cancer, and their usefulness for therapy and diagnosis has encouraged research into the human epigenome. Several biomarker studies have focused on identifying cancer types individually, yet common cancer and multi-cancer markers are still underexplored. We used The Cancer Genome Atlas (TCGA) t...
In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management...
Purpose
As noninvasive biomarkers are an important unmet need for neuroendocrine neoplasms (NEN), biomarker potential of genome-wide molecular profiling of plasma cell-free DNA (cfDNA) was prospectively studied in patients with NEN.
Experimental Design
Longitudinal plasma samples were collected from patients with well-differentiated, metastatic ga...
Several studies have shown that type IV fibrocytes, located in the spiral ligament, degenerate first after noise exposure. Interestingly, this is the region where Coch expression is most abundant. As it is suggested that cochlin plays a role in our innate immune system, our goal is to investigate hearing thresholds and inner ear inflammation after...
ERK1/2 involvement in cell death remains unclear, although many studies have demonstrated the importance of ERK1/2 dynamics in determining cellular responses. To untangle how ERK1/2 contributes to two cell death programs, we investigated ERK1/2 signaling dynamics during hFasL-induced apoptosis and TNF-induced necroptosis in L929 cells. We observed...
Introduction: DFNA9 is characterized by adult-onset progressive senso-rineural hearing loss (SNHL) and vestibular impairment. More than 15 years ago, genotype-phenotype correlation studies estimated the initial age of hearing deterioration in the fourth to fifth decade (ranging from 32 to 43 years). However, these analyses were based on relatively...
To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, a...
Introduction:
DFNA9 is characterized by adult-onset hearing loss and evolution toward bilateral vestibulopathy (BVP). The genotype-phenotype correlation studies were conducted 15 years ago. However, their conclusions were mainly based on symptomatic carriers and the vestibular data exclusively derived from the horizontal (lateral) semicircular can...
Introduction:
DFNA9 is characterized by adult-onset progressive sensorineural hearing loss (SNHL) and vestibular impairment. More than 15 years ago, genotype-phenotype correlation studies estimated the initial age of hearing deterioration in the fourth to fifth decade (ranging from 32 to 43 years). However, these analyses were based on relatively...
Background: Hearing impairment is the most frequent sensory deficit, affecting 466 million people worldwide and has been listed by the World Health Organization (WHO) as one of the priority diseases for research into therapeutic interventions to address public health needs. Inner ear gene therapy is a promising approach to restore sensorineural hea...
The ClinGen Variant Curation Expert Panels (VCEPs) provide disease-specific rules for accurate variant interpretation. Using the hearing loss-specific American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, the Hearing Loss VCEP (HL VCEP) illustrates the utility of expert specifications in varian...
Background
Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.
Methods
Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea ( L.) Moench extract in THP1 monocyte...
Background
Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Due to several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumours is extensively being investigated...
The involvement of genetic factors in the pathogenesis of KC has long been recognized but the identification of variants affecting the underlying protein functions has been challenging. In this study, we selected 34 candidate genes for KC based on previous whole-exome sequencing (WES) and the literature, and resequenced them in 745 KC patients and...
The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease- and kinase-dependent me...
Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm Thalassia testudinum (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model...
Objective:
In this study we aimed to evaluate the predictive cross-sectional sensitivity and longitudinal concordance of a machine-learning algorithm in a series of genetically confirmed p.(Pro51Ser) variant carriers (DFNA9).
Study design:
Cross-sectional study.
Setting:
Tertiary and secondary referral center.
Patients:
Audiograms of 111 sub...
372
Background: Recent studies, including our proof-of-concept study, demonstrated the possibility to detect tumor-derived molecular alterations in cell-free DNA (cfDNA) from plasma of patients with a gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). More in-depth evaluation of the biomarker potential of cfDNA in GEP-NENs is warranted, sinc...
Background:
Advances in gene therapeutic approaches to treat sensorineural hearing loss (SNHL) confront us with future challenges of translating these animal studies into clinical trials. Little is known on patient attitudes towards future innovative therapies.
Objective:
We aimed to better understand the willingness of patients with progressive...
DeaFNess Autosomal Dominant 9 (DFNA9) is a dominant hereditary non-syndromic form of progressive sensorineural hearing loss often associated with vestibular dysfunction. DFNA9 is caused by pathogenic variants in the COCH gene. This gene encodes for cochlin, a protein that is abundantly expressed in the spiral ligament and spiral limbus of the inner...
Cancer cells display DNA hypermethylation at specific CpG islands in comparison with their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promote...
Gasdermin E (GSDME), a gene originally involved in hereditary hearing loss, has been associated with several types of cancer in the last two decades. Recently, GSDME was identified as a pore forming molecule which is activated following caspase‐3‐mediated cleavage resulting in so‐called secondary necrosis following apoptotic cell death, or in prima...
Background:
Confirmation of permanent hearing loss in a newborn should be followed by a search for an underlying etiology because this may impact hearing loss management and counselling.
Methods:
Retrospective chart review of all newborns seen at a tertiary referral center after referral from newborn hearing screening over a 20-year period. The...
Congenital hearing impairment is a sensory disorder that is genetically highly heterogeneous. By performing exome sequencing in two families with congenital nonsyndromic profound sensorineural hearing loss (SNHL), we identified autosomal dominantly inherited missense variants [p.(Asn283Ser); p.(Thr116Ile)] in GREB1L, a neural crest regulatory molec...
DNA methylation is a crucial epigenetic mechanism for gene expression regulation and cell differentiation. Furthermore, it was found to play a major role in multiple pathological processes, including cancer. In pancreatic neuroendocrine neoplasms (PNENs), epigenetic deregulation is also considered to be of significance, as the most frequently mutat...
Background: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.
Methods: A system biology approach involving genomewide transcriptome, epigenome and kinome activity profiles was applied to characterize the immunomodulatory effects of a standardized Echinacea purpurea extract Echi...
Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light of novel blood-based assays. DNA methylation in cancer has been linked to tumorigenesis, but its value as a biomarker has no...
Previous research has shown that genes play a substantial role in determining a person’s susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sa...
High-throughput analysis, including next-generation sequencing and microarrays, have strongly improved our understanding of cancer biology. However, genomic data on rare cancer types, such as neuroendocrine neoplasms, has been lagging behind. Neuroendocrine neoplasms (NENs) develop from endocrine cells spread throughout the body and are highly hete...
Gasdermin E (GSDME), also known as deafness autosomal dominant 5 (DFNA5) and previously identified to be an inducer of regulated cell death, is frequently epigenetically inactivated in different cancer types, suggesting that GSDME is a tumor suppressor gene. In this study, we aimed to evaluate the tumor-suppressive effects of GSDME in two intestina...
Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis. To unravel the contribution of genetic variation in this gene to otosclerosis,...
Background and objectives
The Pro51Ser (P51S) COCH mutation is characterized by a late-onset bilateral sensorineural hearing loss (SNHL) and progressive vestibular deterioration. The aim of this study was to carry out a systematic review of all reported hearing and vestibular function data in P51S COCH mutation carriers and its correlation with age...
In addition to its implication in hereditary hearing loss, the Gasdermin E (GSDME) gene is also a tumor suppressor involved in cancer progression through programmed cell death. GSDME epigenetic silencing through methylation has been shown in some cancer types, but studies are yet to fully explore its diagnostic/prognostic potential in colorectal ca...
The mammalian target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mTOR signalling. The PI3K/Akt/mTOR pathway has a pivotal role in the oncogenesis of neuroendocrine tumours (NETs). In addition, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) drive angiogenesis in NETs...
Purpose:
To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis.
Methods:
We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined...
Background
Detection of tumor-specific alterations in cell-free DNA (cfDNA) has proven valuable as a liquid biopsy for several types of cancer. So far, use of cfDNA remains unexplored for pancreatic neuroendocrine tumor (PNET) patients.
Methods
From 10 PNET patients, fresh frozen tumor tissue, buffy coat and plasma samples were collected. Whole-ex...
Familial clustering of malignant mesothelioma (MM) has been linked to the presence of germline mutations in BAP1. However, families with multiple MM patients, without segregating BAP1 mutation were described, suggesting the existence of other predisposing genetic factors. In this study, we report a previously undescribed Belgian family, in which BA...
Mutations in GJB2, the gene that encodes connexin 26 (Cx26), are the most common cause of sensorineural hearing impairment. The truncating variant 35delG, which determines a complete loss of Cx26 protein function, is the prevalent GJB2 mutation in several populations. Here, we generated and analyzed Gjb2+/- mice as a model of heterozygous human car...
Mutations in DAXX/ATRX, MEN1, and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present...
Objectives:
The purpose of this study is to report the results of a comprehensive etiological work-up for congenitally deaf children including targeted next generation sequencing.
Study design:
Retrospective case review.
Setting:
Tertiary referral center.
Patients:
Fifty children with congenital, bilateral profound hearing loss (HL) (>90 dBn...
Objectives:
Patients diagnosed with malignant pleural mesothelioma (MPM) face a poor prognosis, with an overall survival plateauing at a median of one year. This can be explained by difficulties in early diagnosis, effective treatment and treatment monitoring. Circulating cell-free tumor DNA (ctDNA) is emerging as an interesting biomarker addressi...
High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associa...
Introduction
Breast cancer is the most frequent cancer among women worldwide. Biomarkers for early detection and prognosis of these patients are needed. We hypothesised that DFNA5 (also know as Gasdermin E (GSDME)) may be a valuable biomarker, based upon strong indications for its role as tumour suppressor gene and its function in regulated cell de...
Background
Breast cancer is the most frequent cancer among women worldwide. Biomarkers for early detection and prognosis of these patients are needed. We hypothesized that deafness, autosomal dominant 5 (DFNA5) may be a valuable biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death....
Background
The prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms.
Results
Saliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentia...
Background
Primary tumour location has prognostic impact in metastatic colorectal cancer (mCRC). Here we report retrospective analyses assessing the impact of tumour location on prognosis and efficacy of second-line and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC, and on prognosis in all lines of treatment in patients...
Background
Targeted therapies, although contributing to survival improvement in metastatic colorectal cancer (mCRC), are expensive and may cause side effects. Therefore, confirming that patients are responding to these therapies is extremely important. Currently, follow-up is performed using radiographic evaluation, which has its limitations. Liqui...
Background: Haloplex targeted resequencing is a popular method to analyze both germline and somatic variants in gene panels. However, involved wet-lab procedures may introduce false positives that need to be considered in subsequent data-analysis. No variant filtering rationale addressing amplicon enrichment related systematic errors, in the form o...