title: Familial hematological malignancies: new IDH2 mutation.
abstract: Isocitrate dehydrogenase IDH 1 and IDH 2 mutations were reported in several cancer forms, especially in hematological malignancies, but were never been investigated in familial aggregation. The aim of this study is to determine whether germline isocitrate dehydrogenase genes mutations are involved.We targeted IDH1 and IDH2 genes in 104 familial cases belonging to Tunisian and French populations, including several forms of hematological malignancies and cosegregated solid tumors.We report one IDH1 variant: c.315 G>T, p.Gly105Gly in 15 % of cases, which was assigned to the worst outcome in several studies. Three IDH2 variants were found, among them, one intronic substitution c.543+45 G>A (rs142033117) and two new variants not previously described: c.389 A>T, p.Lys130Met and c.414 T>C, p.Thr138Thr. The p.Lys130Met was found in one case diagnosed with Waldenstrom's disease with familial history of cancer. The enrolled in silico analysis, the functional study, and the absence of this variant in control population strengthen the hypothesis of its deleterious effect.From an extended number of candidate genes analyzed in familial hematological malignancies, IDH2 might be considerably involved since we reported a potential damaging effect.
authors: UR "Biologie moléculaire des leucémies et lymphomes," Laboratoire de Biochimie, Faculté de Médecine de Sousse, Université de Sousse - Tunisie, Avenue Mohamed Karoui, 4002, Sousse, Tunisia. walid_sabrimail@yahoo.fr.
authors: Walid-Sabri
authors: WS
authors: Hamadou
authors: Département d'Oncologie Génétique, de Prévention et Dépistage, Institut Paoli-Calmettes, Marseille, France.
authors: Violaine
authors: V
authors: Bourdon
authors: Centre de Recherche en Cancérologie de Marseille, Centre de référence des mastocytoses, INSERM U1068, Institut Paoli Calmettes, Marseille, France.
authors: Sébastien
authors: S
authors: Létard
authors: Centre de Recherche en Cancérologie de Marseille, Centre de référence des mastocytoses, INSERM U1068, Institut Paoli Calmettes, Marseille, France.
authors: Fabienne
authors: F
authors: Brenet
authors: Laboratoire de Pharmacologie, Faculté de Médecine, Sousse, Tunisia.
authors: Sofien
authors: S
authors: Laarif
authors: UR "Biologie moléculaire des leucémies et lymphomes," Laboratoire de Biochimie, Faculté de Médecine de Sousse, Université de Sousse - Tunisie, Avenue Mohamed Karoui, 4002, Sousse, Tunisia.
authors: Sawsen
authors: S
authors: Besbes
authors: Institut de Cancérologie Gustave Roussy, Villejuif, France.
authors: Angelo
authors: A
authors: Paci
authors: INSERM, U985, Institut Gustave Roussy, Villejuif, France.
authors: Muriel
authors: M
authors: David
authors: INSERM, U985, Institut Gustave Roussy, Villejuif, France.
authors: Virginie
authors: V
authors: Penard-Lacronique
authors: Service d'Hématologie clinique, CHU Farhat Hached, Sousse, Tunisia.
authors: Yosra Ben
authors: YB
authors: Youssef
authors: Service d'Hématologie clinique, CHU Fattouma Bourguiba, Monastir, Tunisia.
authors: Mohamed-Adnène
authors: MA
authors: Laatiri
authors: Département d'Anticipation et de Suivi du Cancer, Centre de Lutte Contre le Cancer - Institut Paoli Calmettes, Marseille, France.
authors: François
authors: F
authors: Eisinger
authors: Service d'Oncologie Génétique, Centre de Lutte Contre le Cancer - Centre Antoine Lacassagne, Nice, France.
authors: Véronique
authors: V
authors: Mari
authors: Service d'Oncologie Génétique, Centre Hospitalier, Niort, France.
authors: Paul
authors: P
authors: Gesta
authors: Institut Sainte Catherine, Avignon, France.
authors: Hélène
authors: H
authors: Dreyfus
authors: Unité de génétique Epidémiologique, Centre Léon Bérard, Lyon, France.
authors: Valérie
authors: V
authors: Bonadona
authors: Centre Eugène Marquis, Rennes, France.
authors: Catherine
authors: C
authors: Dugast
authors: Département de Génétique, Hôpital de la Timone, Marseille, France.
authors: Hélène
authors: H
authors: Zattara
authors: Hôpital d'Enfants, CHU de Dijon, Dijon, France.
authors: Laurence
authors: L
authors: Faivre
authors: Département d'Oncologie Génétique, de Prévention et Dépistage, Institut Paoli-Calmettes, Marseille, France.
authors: Testsuro
authors: T
authors: Noguchi
authors: INSERM, U985, Institut Gustave Roussy, Villejuif, France.
authors: Abderrahim
authors: A
authors: Khélif
authors: Laboratoire de Pharmacologie, Faculté de Médecine, Sousse, Tunisia.
authors: Chaker Ben
authors: CB
authors: Salem
authors: Centre de Recherche en Cancérologie de Marseille, Centre de référence des mastocytoses, INSERM U1068, Institut Paoli Calmettes, Marseille, France.
authors: Patrice
authors: P
authors: Dubreuil
authors: Département d'Oncologie Génétique, de Prévention et Dépistage, Institut Paoli-Calmettes, Marseille, France.
authors: Hagay
authors: H
authors: Sobol
authors: UR "Biologie moléculaire des leucémies et lymphomes," Laboratoire de Biochimie, Faculté de Médecine de Sousse, Université de Sousse - Tunisie, Avenue Mohamed Karoui, 4002, Sousse, Tunisia.
authors: Zohra
authors: Z
authors: Soua
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase
keywords: Familial hematological malignancies; Germline mutation; IDH1; IDH2