Store

Research

Christina Antonescu, MD
Memorial Sloan-Kettering
“Investigating Oncogenic Mechanisms in Angiosarcoma”
 Previous Major Accomplishments:  
  1. Identification of activating KDR (VEGFR2) mutations in 10% of angiosarcoma, including primary breast and radiation-associated (Antonescu, Cancer Research 2009).
 
  1. Identification of MYC amplification in overwhelming majority of secondary AS (radiation and lymphedema-associated)(Guo T, Genes Chromosome Cancer 2011). A smaller subset of secondary AS (25%) were shown to have co-amplification of FLT4 (VEGFR3). A subsequent study has shown that 10% of primary AS (mainly breast and bone) may also show MYC amplification (Italiano, Genes Chromosome Cancer 2012).
 
  1. Defined the pathogenesis of radiation-associated atypical vascular lesion (AVL), lacking MYC gene amplifications. AVL occurs in the same patient population with secondary AS and often represents a diagnostic challenge. Our study supports that AVL is a distinct entity with benign behavior and does not represent a precursor lesion to AS development (Guo T, genes Chromosomes Cancer 2011).
 
  1. MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis. (Italiano, Genes Chromosomes Cancer 2012)
 
  1. AS constitute a distinct subgroup among sarcomas with complex genomics showing rare p53 and PTEN mutations (Italiano, Cancer 2012).
 
  1. Defined novel translocations in malignant and atypical epithelioid vascular tumors that are typically considered in the differential diagnosis of AS. These new gene fusions represent extremely useful molecular markers for a correct classification of vascular tumors:
    • Epithelioid hemangioendothelioma:
      1. WWTR1-CAMTA1 (Errani, Genes Chromosomes Cancer 2011);
      2. YAP1-TFE3 (Antonescu CR, Genes Chromosomes Cancer 2013)
    • Atypical epithelioid hemangioma: ZFP36-FOSB (Antonescu CR, Genes Chromosomes Cancer 2014)
 
  1. Investigator-initiated clinical trial in angiosarcoma sponsored by the Alliance group (Alliance A091103): A Phase II study of the angiopoietin-1 and -2 peptibody trebananib for the treatment of angiosarcoma – based on our genomic/gene expression data (PI Dr Sandra D’Angelo, MSKCC Sarcoma Service).
     
Profile
Research Funded By
Cycle for Survival Donations