Abstract 2017: Exome sequencing reveals novel mutations in a GIST and a paraganglioma occurring simultaneously in a patient with complete form of Carney triad.

Abstract

Abstract Carney triad is a rare syndrome which is defined by the occurrence of multicentric gastric GIST, paraganglioma and pulmonary chondroma. In contrast to the closely-related Carney-Stratakis syndrome (CSS), Carney syndrome is not inherited. In both syndromes, the tumors are characterized by a loss of Succinate Dehydrogenase B protein (so-called SDHB-deficient tumors). Only recently, inactivating mutations in the SDH subunits A, B, C, and D have been found to be present in the majority of SDHB-deficient GISTs of CSS, but not in GISTs in the setting of Carney triad. We performed exome sequencing of DNA samples derived from blood as well as of the GIST and the paraganglioma from a female patient with a complete Carney triad. Additionally, the genome from the blood DNA was sequenced at high coverage, and low coverage genomes of both tumor DNAs were evaluated for copy number variations. SDHA and B mRNA and protein expression were analysed by qRT-PCR and Western Blot analysis, respectively. Both the GIST and the paraganglioma from the Carney patient were negative for SDHB by immunohistochemistry, and did not display noticeable levels of SDHB in the Western Blot analysis. In contrast, SDHB mRNA levels were equal to SDHA levels, and also to GISTs from sporadic GISTs with KIT mutations. Exome sequencing revealed 10 and 18 somatic missense mutations in the DNA from the GIST and the paraganglioma, which were not present in the DNA from the blood. Additionally, one somatic insertion/deletion was found in each tumor. These novel mutations will provide better insights in our understanding of this rare albeit fascinating disease, and might also be suitable as targets for future therapies. Citation Format: Florian Haller, Abbas Agaimy, Evgeny A. Moskalev, Natalie Jäger, Benedikt Broers, Stefan Wiemann, Arndt Hartmann. Exome sequencing reveals novel mutations in a GIST and a paraganglioma occurring simultaneously in a patient with complete form of Carney triad. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2017. doi:10.1158/1538-7445.AM2013-2017