TY - JOUR
T1 - Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations
AU - Pantaleo, Maria A.
AU - Lolli, Cristian
AU - Nannini, Margherita
AU - Astolfi, Annalisa
AU - Indio, Valentina
AU - Saponara, Maristella
AU - Urbini, Milena
AU - La Rovere, Stefano
AU - Gill, Antony
AU - Goldstein, David
AU - Ceccarelli, Claudio
AU - Santini, Donatella
AU - Rossi, Giulio
AU - Fiorentino, Michelangelo
AU - Di Scioscio, Valerio
AU - Fusaroli, Pietro
AU - Mandrioli, Anna
AU - Gatto, Lidia
AU - Catena, Fausto
AU - Basso, Umberto
AU - Ercolani, Giorgio
AU - Pinna, Antonio Daniele
AU - Biasco, Guido
PY - 2015/5/8
Y1 - 2015/5/8
N2 - 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.
AB - 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.
KW - Gastrointestinal stromal tumors
KW - SDH deficient
KW - SDHA
KW - succinate dehydrogeanase
KW - wild-type
UR - http://www.scopus.com/inward/record.url?scp=84928898398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928898398&partnerID=8YFLogxK
U2 - 10.1038/gim.2014.115
DO - 10.1038/gim.2014.115
M3 - Article
C2 - 25188872
AN - SCOPUS:84928898398
VL - 17
SP - 391
EP - 395
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
IS - 5
ER -