AN INTEGRATED ANALYSIS OF GENETIC AND EPIGENETIC ALTERATIONS IN GASTROINTESTINAL STROMAL TUMORS REVEALS DISTINCT CLINICAL PHENOTYPES Sosipatros A. Boikos , Suzanne George, Katherine A. Janeway, Keith J. Killian, Su Young Kim, Michael P. LaQuaglia, Lauren Long, Paul S. Meltzer, Markku M. Miettinen, Karel Pacak, Alberto Pappo, Margarita Raygada, Joshua Schiffman, Constantine Stratakis, Jonathan Trent, Margaret Von Mehren, Christopher B. Weldon, Jennifer Wright, Lee J. Helman On behalf of the Consortium for Pediatric & wildtype GIST Research October 31, 2013 Connective Tissue Oncology Society
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AN INTEGRATED ANALYSIS OF GENETIC AND EPIGENETIC ALTERATIONS IN GASTROINTESTINAL STROMAL TUMORS
REVEALS DISTINCT CLINICAL PHENOTYPES
Sosipatros A. Boikos, Suzanne George, Katherine A. Janeway, Keith J. Killian, Su Young Kim, Michael P. LaQuaglia, Lauren Long, Paul S. Meltzer, Markku M. Miettinen, Karel Pacak, Alberto Pappo, Margarita Raygada, Joshua Schiffman, Constantine Stratakis, Jonathan Trent, Margaret Von Mehren, Christopher B. Weldon, Jennifer Wright, Lee J. Helman
On behalf of the Consortium for Pediatric & wildtype GIST Research
October 31, 2013Connective Tissue Oncology Society
NO DISCLOSURES
Overview
• Presentation of the most recent genetic and clinical findings of the NIH Pediatric and Wildtype GIST clinic.
Overview
• Presentation of the most recent genetic and clinical findings of the NIH Pediatric and Wildtype GIST clinic.
• Correlation of the genetic and epigenetic findings with the clinical phenotype
Overview
• Presentation of the most recent genetic and clinical findings of the NIH Pediatric and Wildtype GIST clinic.
• Correlation of the genetic and epigenetic findings with the clinical phenotype
• Discussion
Wild-Type GIST
• 85% of GIST occurring in young population is lacking mutations in KIT or PDGFRA
Wild-Type GIST
• 85% of GIST occurring in young population is lacking mutations in KIT or PDGFRA
• Stomach location, epithelioid histology
Wild-Type GIST
• 85% of GIST occurring in young population is lacking mutations in KIT or PDGFRA
• Stomach location, epithelioid histology• May be syndromic (Carney Triad, Stratakis-
Carney Syndrome)
Wild-Type GIST
• 85% of GIST occurring in young population is lacking mutations in KIT or PDGFRA
• Stomach location, epithelioid histology• May be syndromic (Carney Triad, Stratakis-
Carney Syndrome)• Tyrosine kinase inhibition is less effective
compared to KIT or PDGFRA mutant tumors
Wild-Type GIST
• 85% of GIST occurring in young population is lacking mutations in KIT or PDGFRA
• Stomach location, epithelioid histology• May be syndromic (Carney Triad, Stratakis-
Carney Syndrome)• Tyrosine kinase inhibition is less effective
compared to KIT or PDGFRA mutant tumors• Mutations in Succinate Dehydrogenase (SDH)
genes have been found in some but not in all patients
10 WT GIST clinics; 115 patients have been seen till An international clinic twice a year115 patients have been seen in 10 clinics since 2008.
Objectives of the Wildtype Clinic at NIH
•To bring together healthcare providers who have the most experience treating and studying GIST•To obtain clinical history, response to prior treatments, histopathologic results, radiographic assessments and genetic/molecular analyses•Continue long-term follow-up for these patients
Summary of Mutation Analysis of 78 Patients with Wild-Type GIST Fully Analyzed for SDH, BRAF, and NF1 Mutations