title: Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma.
abstract: We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5 mg/m2given intravenously over 24 hours every 21 days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy.
authors: a Division of Medical Oncology B , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Gianmaria
authors: G
authors: Miolo
authors: b Division of Experimental Oncology 1 , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Alessandra
authors: A
authors: Viel
authors: c Department of Diagnostic Laboratories and Cell Therapy, Division of Pathology , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Vincenzo
authors: V
authors: Canzonieri
authors: d Nuclear Medicine Unit, IRCCS National Cancer Institute (CRO) , Aviano , Italy.
authors: Tania
authors: T
authors: Baresic
authors: a Division of Medical Oncology B , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Angela
authors: A
authors: Buonadonna
authors: e Department of Oncology, Division of Medical Oncology , Sassari Hospital , Sassari , Italy.
authors: Davide Adriano
authors: DA
authors: Santeufemia
authors: b Division of Experimental Oncology 1 , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Della Puppa
authors: DP
authors: Lara
authors: f Department of Translational Research , IRCCS, National Cancer Institute (CRO) , Aviano , Italy.
authors: Giuseppe
authors: G
authors: Corona
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D004149:Dioxoles / Q000008:administration & dosage; D016889:Endometrial Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D020125:Mutation, Missense; D018203:Sarcoma, Endometrial Stromal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D015251:Epirubicin; D000077606:Trabectedin; D007069:Ifosfamide
keywords: BRCA2 germline variant; DNA damage; mutations; soft tissue sarcoma; trabectedin; tumor genotype