Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment. (Articolo in rivista)

Type
Label
  • Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment. (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1093/jnci/dju182 (literal)
Alternative label
  • Sadow P.M.; Priolo C.; Nanni S.; Karreth F.A.; Duquette M.; Martinelli R.; Husain A.; Clohessy J.; Kutzner H.; Mentzel T.; Carman CV.; Farsetti A.; Henske E.P.; Palescandolo E.; Macconaill L.E.; Chung S.; Fadda G.; Lombardi C.P.; De Angelis A.M.; Durante O.; Parker J.A.; Pontecorvi A.; Dvorak H.F.; Fletcher C.; Pandolfi P.P.; Lawler J.; Nucera C. (2014)
    Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment.
    in Journal of the National Cancer Institute. Monographs
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Sadow P.M.; Priolo C.; Nanni S.; Karreth F.A.; Duquette M.; Martinelli R.; Husain A.; Clohessy J.; Kutzner H.; Mentzel T.; Carman CV.; Farsetti A.; Henske E.P.; Palescandolo E.; Macconaill L.E.; Chung S.; Fadda G.; Lombardi C.P.; De Angelis A.M.; Durante O.; Parker J.A.; Pontecorvi A.; Dvorak H.F.; Fletcher C.; Pandolfi P.P.; Lawler J.; Nucera C. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 106 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 8 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Pathology, Massachusetts General Hospital (PMS) and Department of Medicine, Brigham and Women's Hospital (CP, EPH), Harvard Medical School, Boston, MA; Unit of Endocrinology, Department of Medicine, A. Gemelli, Catholic University, Roma, Italy (SN, AP); Division of Cancer Genetics, Department of Medicine (FAK, JC, PPP) and Laboratory of Human Thyroid Cancers Preclinical and Translational Research, Division of Cancer Biology and Angiogenesis, Department of Pathology, Center for Vascular Biology Research (MD, CN), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Medicine (RM, CVC) and Department of Pathology (AH, HD, JL), Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA; Dermatopathologische Gemeinschaftspraxis, Siemensstrasse, Friedri chshafen, Germany (HK, TM); National Research Council (CNR-IBCN) and Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy (AF); Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (EP, LEM); MIT/Broad Institute, Cambridge, MA (EP, LEM); Department of Plastic and Reconstructive Surgery, National Health Insurance Service Ilsan Hospital, Ilsan, Korea (SC); Department of Pathology (GF) and Department of Surgery (CPL), A. Gemelli, Catholic University, Roma, Italy; Department of Experimental and Clinical Medicine (AMDA) and Unit of Radiotherapy (OD), University of Catanzaro, Italy; Department of Nuclear Medicine, Beth Israel Deaconess Medical Center (JAP); Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (CF). (literal)
Titolo
  • Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment. (literal)
Abstract
  • Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects in BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)-dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely followed because of the risk for multifocality/recurrence. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it