Investigadoras do i3S definem orientações para síndrome rara de cancro gástrico

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Investigadoras do i3S definem orientações para síndrome rara de cancro gástrico

Sexta, 30.10.2020

Um consórcio mundial de especialistas, do qual fazem parte três grupos de investigação do Instituto de Investigação e Inovação em Saúde da Universidade do Porto (i3S), acaba de publicar na revista científica Lancet Oncology as novas orientações internacionais de diagnóstico, prevenção e tratamento da Síndrome de Cancro Gástrico Difuso Hereditário (HDGC). O artigo surge na sequência da reunião de trabalho que juntou especialistas de todo o mundo (geneticistas, investigadores básicos, cirurgiões, profissionais de aconselhamento genético, oncologistas, nutricionistas, farmacologistas…) para discutir o conhecimento atual sobre esta síndrome ligada ao gene da Caderina-E, CDH1.

 

«Duas décadas depois de ter sido identificada a base genética para a síndrome HDGC, juntámo-nos para definir novas orientações clínicas e aproveitámos para debater a expansão da causa da doença a um novo gene (CTNNA1), assim como os sinais de suspeita clínica a novas apresentações, nomeadamente malformações congénitas e um tipo de cancro da mama, especificamente associado à perda de Caderina-E», explica Raquel Seruca, líder do grupo de investigação do i3S «Epithelial Interactions in Cancer».

 

Este encontro na Nova Zelândia, acrescenta Carla Oliveira, líder do grupo «Expression Regulation in Cancer», contou com a participação especial de famílias portadoras de mutações no gene CDH1, incluindo as primeiras a serem descritas no artigo que reporta a descoberta da síndrome. «A presença das famílias nesta reunião fez deste encontro uma ocasião especial, criando a oportunidade para ouvir testemunhos clínicos reais, e na primeira pessoa, mas também para mostrar aos que sofrem da doença os contributos importantes de muitos cientistas e profissionais de saúde», acrescenta.

 

Os investigadores do i3S/Ipatimup têm tido um papel ativo e fundamental desde o primeiro dia no consórcio mundial que estuda esta doença. É o caso da patologista Fátima Carneiro, do grupo de investigação do i3S «Intercellular Communication and Cancer», qe foi a primeira a descrever as características microscópicas da doença no estômago e é atualmente consultora mundial na área desta patologia. Raquel Seruca e Joana Figueiredo, do grupo «Epithelial Interactions in Cancer», têm focado a sua atenção na descoberta dos mecanismos de invasão ligados à perda de função da proteína Caderina-E, usando um tipo particular de mutações. A investigadora Carla Oliveira, por seu lado, tem centrado o seu trabalho na descoberta de novas causas de doença hereditária, liderando atualmente um projeto europeu sobre este tema.

 

«O produto do trabalho destes três grupos de investigação no i3S tem sido fundamental para avançar na compreensão da doença, no seu rastreio e diagnóstico precoce, na prevenção e no tratamento», sublinha Joana Figueiredo, do grupo «Epithelial Interactions in Cancer».

O artigo científico agora publicado, adianta Fátima Carneiro, representa «uma ferramenta essencial que ajudará os clínicos e os doentes de todo o mundo que um dia sejam confrontados com o diagnóstico desta doença». No plano da investigação, acrescenta Raquel Seruca, «a aposta no estudo desta doença, de forma complementar por um conjunto de cientistas do mesmo instituto, tem sido um sucesso e projeta a instituição e a investigação portuguesa ao mais alto nível».

 

Autores e Afiliações:

Vanessa RBlairFRACSab MaybelleMcLeodc ProfFátimaCarneiroMDd ProfDaniel GCoitMDe Johanna LD'AddarioMHSf Jolanda Mvan DierenMDgKirsty LHarrisBPharmh ProfNicolineHoogerbruggeMDiProfCarlaOliveiraPhDd Rachel Svan der PostMDj JulieArnoldl Patrick RBenusiglioMDo Tanya MBisselingMDk ProfAlexBoussioutasMBBSp AnnemiekeCatsMDg AmandaCharltonMBChBm Karen E ChelcunSchreiberf Jeremy LDavisMDq Massimiliano diPietroMDr ProfRebecca CFitzgeraldMDr ProfJames MFordMDtKimberleyGametn IreneGulloMDd Richard HHardwickFRCSuProfDavid GHuntsmanMDv PardeepKaurahPhDwx Sonia SKupferMDyAndrewLatchfordMDzaa ProfPaul FMansfieldMDab TakeshiNakajimaMDacSusanParryMBChBlJeremyRossaakFRACSadProfHaruhikoSugimuraMDaf ProfMagaliSvrcekMDag MarcTischkowitzMDs ToshikazuUshijimaMDah HidetakaYamadaPhDaf ProfHan-KwangYangai AdrianClaydonMBChBae JoanaFigueiredoPhDd KarynParingataiPhDaj ProfRaquelSerucaPhDd NicolaBougen-ZhukovPhDak TomBrewMScak SimoneBusijaam PatriciaCarneiroPhDd LynnDeGregorioMBAan HelenFisherDipEdh ErinGardnerc Tanis DGodwinMScak Katharine NHolmBSao BostjanHumarPhDap Caroline JLintottPhDaq Elizabeth CMonroeMSan Mark DMullerMBChBar EnriqueNoreroMDas YasminNouriMScak JoanaParedesPhDd João MSanchesPhDat EmilySchulpenBSc [Hons]ak Ana SRibeiroPhDd AndrewSporleMAal JamesWhitworthPhDs LiyingZhangMDau ProfAnthony EReevePhDak ProfParryGuilfordPhDak

 

a Department of Surgery, University of Auckland, Auckland, New Zealand

b St Marks Breast Centre, Auckland, New Zealand

c Kimihauora Health and Research Clinic, Mt Maunganui, New Zealand

d Instituto de Investigação e Inovação em Saúde & Institute of Molecular Pathology and Immunology of the University of Porto, Department of Pathology, University of Porto, Porto, Portugal

e Memorial Sloan Kettering Cancer Center and Weill Cornell Medical School, New York, NY, USA

f HereditaryDiffuseGastricCancer.org, Madison, WI, USA

g Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands

h Brisbane, QLD, Australia

i Department of Human Genetics, Radboud University Medical Centre, Nijmegen, Netherlands

j Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

k Department of Gastroenterology, Radboud University Medical Centre, Nijmegen, Netherlands

l New Zealand Familial Gastrointestinal Cancer Service, Auckland Hospital, Auckland, New Zealand

m Department of Histopathology, Auckland Hospital, Auckland, New Zealand

n Genetic Health Service New Zealand Northern Hub, Auckland Hospital, Auckland, New Zealand

o Consultation d'Oncogénétique, Unité Fonctionnelle d'Oncogénétique, Département de Génétique, DMU BioGeM, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France

p Department of Medicine, Royal Melbourne Hospital and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

q Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

r Medical Research Council Cancer Unit, University of Cambridge, Cambridge, UK

s Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

t Division of Oncology, Departments of Medicine and Genetics, Stanford University School of Medicine, Stanford, CA, USA

u Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK

v Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

w Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

x Hereditary Cancer Program, British Columbia Cancer, Vancouver, BC, Canada

y Section of Gastroenterology, Nutrition and Hepatology, University of Chicago, Chicago, IL, USA

z St Mark's Hospital, London, UK

aa Department of Cancer and Surgery, Imperial College, London, UK

ab University of Texas MD Anderson Cancer Center, Houston, TX, USA

ac Department of Clinical Genetic Oncology, Cancer Institute Hospital, Tokyo, Japan

ad Department of Surgery, Tauranga Hospital, Tauranga, New Zealand

ae Department of Gastroenterology, Tauranga Hospital, Tauranga, New Zealand

af Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

ag Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Department of Pathology, Hôpital Saint-Antoine, Paris, France

ah Division of Epigenomics, National Cancer Centre Research Institute, Tokyo, Japan

ai Seoul National University Hospital, Seoul, South Korea

aj Te Tumu School of Māori, Pacific and Indigenous Studies, University of Otago, Dunedin, New Zealand

ak Cancer Genetics Laboratory, Te Aho Matatū, Department of Biochemistry, University of Otago, Dunedin, New Zealand

al Healthier Lives National Science Challenge, University of Otago, Dunedin, New Zealand

am No Stomach for Cancer, Madison, WI, USA

an DeGregorio Family Foundation, New York, NY, USA

ao Department of Biochemistry and Molecular Medicine, University of California Davis School Of Medicine, Davis, CA, USA

ap Laboratory of the Swiss Hepato-Pancreato-Biliary and Transplantation Centre, Department of Surgery, University Hospital Zürich, Zurich, Switzerland

aq Genetic Health Service New Zealand South Island Hub, Christchurch Hospital, Christchurch, New Zealand

ar Mt Maunganui, New Zealand

as Esophagogastric Surgery Unit, Digestive Surgery Department, Hospital Dr Sotero del Rio, Pontificia Universidad Catolica de Chile, Santiago, Chile

at Institute for Systems and Robotics, Instituto Superior Técnico, Lisbon, Portugal

au Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

 

Abstract:

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of families with HDGC. In this Policy Review, we present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC), which recognise the emerging evidence of variability in gastric cancer risk between families with HDGC, the growing capability of endoscopic and histological surveillance in HDGC, and increased experience of managing long-term sequelae of total gastrectomy in young patients. To redress the balance between the accessibility, cost, and acceptance of genetic testing and the increased identification of pathogenic variant carriers, the HDGC genetic testing criteria have been relaxed, mainly through less restrictive age limits. Prophylactic total gastrectomy remains the recommended option for gastric cancer risk management in pathogenic CDH1 variant carriers. However, there is increasing confidence from the IGCLC that endoscopic surveillance in expert centres can be safely offered to patients who wish to postpone surgery, or to those whose risk of developing gastric cancer is not well defined.

 

Revista: The Lancet Oncology

 

Linkhttps://www.sciencedirect.com/science/article/pii/S1470204520302199?dgcid=author