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Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations

Genet Med. 2014 Sep 4.

Author

Pantaleo MA, Lolli C, Nannini M, Astolfi A, Indio V, Saponara M, Urbini M, La Rovere S, Gill A, Goldstein D, Ceccarelli C, Santini D, Rossi G, Fiorentino M, Di Scioscio V, Fusaroli P, Mandrioli A, Gatto L, Catena F, Basso U, Ercolani G, Pinna AD, Biasco G.

Abstract

Purpose: A subset of patients with KIT/PDGFRA wild-type gastrointestinal stromal tumors show loss of function of succinate dehydrogenase, mostly due to germ-line mutations of succinate dehydrogenase subunits, with a predominance of succinate dehydrogenase subunit A. The clinical outcome of these patients seems favorable, as reported in small series in which patients were individually described. This work evaluates a retrospective survival analysis of a series of patients with metastatic KIT/PDGFRA wild-type succinate dehydrogenase-deficient gastrointestinal stromal tumors.

Methods: Sixty-nine patients with metastatic gastrointestinal stromal tumors were included in the study (11 KIT/PDGFRA wild-type, of whom 6 were succinate dehydrogenase deficient, 5 were non-succinate dehydrogenase deficient, and 58 were KIT/PDGFRA mutant). All six succinate dehydrogenase-deficient patients harbored SDHA mutations. Kaplan-Meier curves and log-rank tests were used to compare the survival of patients with succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors with that of KIT/PDGFRA wild-type patients without succinate dehydrogenase deficiency and patients with KIT/PDGFRA-mutant gastrointestinal stromal tumors.

Results: Follow-up ranged from 8.5 to 200.7 months. The difference between succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors and KIT/PDGFRA-mutant or KIT/PDGFRA wild-type non-succinate dehydrogenase deficient gastrointestinal stromal tumors was significant considering different analyses (P = 0.007 and P = 0.033, respectively, from diagnosis of gastrointestinal stromal tumor for the whole study population; P = 0.005 and P = 0.018, respectively, from diagnosis of metastatic disease for the whole study population; P = 0.007 for only patients who were metastatic at diagnosis).

Conclusion: Patients with metastatic KIT/PDGFRA wild-type succinate dehydrogenase-deficient gastrointestinal stromal tumors harboring succinate dehydrogenase subunit A mutations present an impressively long survival. These patients should be identified in clinical practice to better tailor treatments and follow-up over time.Genet Med advance online publication 04 September 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.115.

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