Veronique Bataille

• MD PhD FRCP
• Consultant at King's College London

Background Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated...

Whole-skin DNA methylation variation has been implicated in several diseases, including melanoma, but its genetic basis has not yet been fully characterized. Using bulk skin tissue samples from 414 healthy female UK twins, we performed twin-based heritability and methylation quantitative trait loci (meQTL) analyses for >400,000 DNA methylation site...

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced...

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81...

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the Interna...

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology d...

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome dynamics during ICB is urgently needed. Through longitudinal shotgun metagenomics profiling in 175 patients treated with ICB for ad...

Background: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i treated patients. Severe cutaneous irAE do not often occur but could be life-thre...

Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids’ structure and functions. Tumours a...

Importance: Immune checkpoint blockade (ICB) has improved the survival of patients with advanced melanoma. Durable responses are observed for 40% to 60% of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with ICB, and patients experience a range of immune-related adverse events of d...

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N=1,086,394, replication N=3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 n...

Background Inflammation can modulate tumour growth and progression, and influence clinical response to treatment. We investigated the potential of circulating inflammatory proteins for response stratification of immune checkpoint inhibitor (ICI) therapy for advanced melanoma. Methods Study subjects were 87 patients with unresectable stage III or I...

A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and...

Background: Symptoms of SARS-CoV-2 infection have differed during the different waves of the pandemic, but little is known about how cutaneous manifestations have changed. Objectives: Investigate the diagnostic value, frequency, and duration of cutaneous manifestations of SARS-CoV-2 infection and explore their variations between the Delta and Om...

Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell...

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was forme...

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five ob...

We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP–CpG associations (methylation quantitative trait loci (meQTL), P < 10⁻¹⁴), including 467,915 meQTL that operate in trans. The meQTL are enriched for functionally relevant char...

Linked Article: Català et al. Br J Dermatol 2022; 186:142–152.

The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and pro...

Purpose Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach. Methods Whole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplication...

Background One of the challenging aspects of SARS‐CoV‐2 infection is its diverse multi‐systemic disease presentation. Objectives Evaluate the diagnostic value of cutaneous manifestations of SARS‐CoV‐2 infection and investigate their duration and timing in relation to other COVID‐19 symptoms Methods We used data from 336,847 UK users of the COVID...

Five patients receiving checkpoint inhibitor immunotherapy (CPI) under our care across two cancer centers over a 12-month period have subsequently developed campylobacterosis. All had received immune-suppressive treatment for CPI-related colitis in the weeks or months preceding the detection of Campylobacter infection, with negative stool cultures...

Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the imp...

Despite growing public awareness of the adverse consequences of excessive sun exposure, modifying sun-seeking behavior is challenging because it appears to be driven by addictive mechanisms. This can have effects on health because sun exposure, although beneficial, when prolonged and repeated shows a causal relationship with skin cancer risk. Using...

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since...

Background The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. Objective Members of the E...

SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collecte...

Abstract is missing (Short Communication)

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical region...

Background Naevi number change with age.Thus, a better understanding of naevus biology will shed more light on the genetic and environmental factors for melanoma development. Methods The study is a prospective two‐wave study based on adult twins from the TwinsUK registry(n=414) who underwent a total body naevus counts with an interval of at least...

There is increasing evidence that the behaviour of naevi and melanoma is under significant genetic and/or epigenetic control. Melanoma tumours behaves similarly all over the world. Many genes have now been implicated in melanoma risk and naevi number. Embryogenesis has also been important in the discovery of links between several neurological disea...

In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was for...

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of m...

Cutaneous melanomas are excised with 1- to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumour thickness 1.0 mm or 0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients sh...

A unique collaboration of multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' exp...

A 67-year-old woman presented in 2012 with a crusty nodule on the left lower limb. Histopathological examination at this time reported a poorly differentiated squamous cell carcinoma (SCC). Two years later, she underwent lymphadenectomy and radiotherapy due to unilateral inguinal and pelvic sidewall nodal metastases. The following year she required...

Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an...

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer collaborated to develop recommendations on diagnosis and treatment of BCC. A new classifica...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Much of the heredity of melanoma remains unexplained. Using an unbiased whole genome screening approach for copy number we identify here a novel melanoma predisposing factor, familial duplications of gene PPP2R3B, encoding a regulatory unit of critical phosphatase PP2A. Significant correlation between expression of PPP2R3B in tumour tissue and surv...

The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify...

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analy...

Background Many melanoma observational studies have been carried out across different countries and geographic areas using heterogeneous assessments of epidemiologic risk factors and clinical variables. Aim To develop a consensus questionnaire to standardize epidemiologic and clinical data collection for melanoma risk assessment. Methods We used...

The presence of a skin‐brain connection whereby alterations in the skin can inform on mechanisms underlying neurodegenerative diseases is increasingly recognized. In this study, we used a discovery (n=321) and replication (n=147) sample from the TwinsUK population to test the association between naevus count and memory function, and its mediation b...

The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and rep...

Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but...

As for all types of cancer, the incidence of melanoma increases with age. However, naevus counts (the principal risk factor for melanoma) decrease with age; hence the relationship between ageing and melanoma is complex. Subjects who maintain a high naevus count after the age of 50 years are more likely to be affected by melanoma, as their lesions d...

Background: Sentinel lymph node (SLN)-positive melanoma patients are a heterogeneous group of patients with survival rates ranging from ∼20 to over 80%. No data are reported concerning the role of histological regression on survival in stage III melanoma. Methods: The study included 365 patients with positive SLN from two distinct hospitals. The...

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, United Kingdom, and United States, comprising a total of 52,506 phenotyped individuals. We confirm known loci including MTAP , PLA2G6 , and IRF4 , and detect novel SNPs at...

e21010 Background: Despite significant gains from systemic immunotherapy, prompt recognition and management of immune related adverse events (irAEs) remains key to minimising acute and chronic morbidity, and can sometimes allow treatment to be re-initiated. Active management of irAEs is corticosteroid based, with additional immunosuppressants used...

Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of...

Background: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. Objective: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. Methods: A questionnaire was sent via mail to clinicians involved in melan...

High naevus count is the strongest risk factor for melanoma and although gene variants have been discovered for both traits, epigenetic variation is unexplored. We investigated 322 healthy human skin DNA methylomes associated with total body naevi count, incorporating genetic and transcriptomic variation. DNA methylation changes were identified at...

Lower Vitamin D serum levels are linked to increased melanoma risk and poorer survival. Naevus counts are associated with both melanoma risk and survival and to leucocyte telomere length. Vitamin D is also linked to telomere biology with higher levels of Vitamin D in individuals with longer leucocyte telomere length despite adjusting for age. Using...

The MC1R gene plays a crucial role in pigmentation synthesis. Loss-offunction MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cut...

In transit metastases (ITM) from extremity or trunk melanomas are subcutaneous or cutaneous lymphatic deposits of melanoma cells, distant from the primary site but not reaching the draining nodal basin. Superficial ITM metastases develop in 5–10% of melanoma patients and are thought to be caused by cells spreading along lymphatics; ITM appear biolo...

Naevus count is the most predictable phenotypic risk factor for melanoma and is mainly influenced by genetic factors1,2,3. Melanoma disparities according to gender have been reported in many studies in term of body distribution, survival and to a lesser extent incidence1,2. It is well established that women are more likely to get melanoma on the lo...

The field of melanoma genetics is moving at great pace with new platforms to investigate single nucleotide polymorphism, genome sequencing, gene expression, and methylation. Melanoma incidence is still rising mainly because of screening campaigns, which has increased the number of reported melanomas. However, mortality due to melanoma is not decrea...

The management of melanoma is constantly evolving. New therapies and surgical advances have changed the landscape over the last years. Since being introcuced by Dr Donald Morton, the role of sentinel lymph node has been debated. In many melanoma centres, sentinel node biopsy is not a standard of care for melanoma above 1 mm in thickness. The result...

Background: Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy. Methods: The survey was designed to investigate the opinions of melanoma physicians on decision...

New therapies for advanced melanoma have led to major advances, which, for the first time, showed improved survival for patients with this very challenging neoplasm. These new treatments are based on gene-targeted therapies or stimulation of immune responses. However, these treatments are not without challenges in terms of resistance and toxicity....

To increase our understanding of the genetic basis of adiposity and its links to cardiometa- bolic disease risk, we conducted a genome-wide association meta-analysis of body fat per- centage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (Po5􏰀10􏰁8), of which eight were previously associated with increased overall a...

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (Po5�10�8), of which eight were previously associated with increased overall adipo...

Supplementary Figures 1-8, Supplementary Tables 1-26 and Supplementary Notes 1-3.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, Af...