A Novel Kindred with Familial Gastrointestinal Stromal Tumors Caused by a Rare KIT Germline Mutation (N655K): Clinico-Pathological Presentation and TKI Sensitivity

被引:14
作者
Fornasarig, Mara [1 ]
Gasparotto, Daniela [2 ]
Foltran, Luisa [3 ]
Campigotto, Michele [4 ]
Lombardi, Sara [2 ]
Del Savio, Elisa [2 ]
Buonadonna, Angela [3 ]
Puglisi, Fabio [3 ,5 ]
Sulfaro, Sandro [6 ]
Canzonieri, Vincenzo [4 ,7 ]
Cannizzaro, Renato [1 ]
Maestro, Roberta [2 ]
机构
[1] IRCCS, Ctr Riferimento Oncol Aviano CRO Aviano, Unit Oncol Gastroenterol, I-33081 Aviano, Italy
[2] IRCCS, Ctr Riferimento Oncol Aviano CRO Aviano, Unit Oncogenet & Funct Oncogen, I-33081 Aviano, Italy
[3] IRCCS, Ctr Riferimento Oncol Aviano CRO Aviano, Unit Med Oncol & Canc Prevent, I-33081 Aviano, Italy
[4] Univ Trieste, Dept Med Surg & Hlth Sci, I-34127 Trieste, Italy
[5] Univ Udine, Dept Med, I-3310 Udine, Italy
[6] Santa Maria Degli Angeli Gen Hosp, Unit Pathol, I-33170 Pordenone, Italy
[7] IRCCS, Unit Pathol, Ctr Riferimento Oncol Aviano CRO Aviano, I-33081 Aviano, Italy
关键词
GIST; gastrointestinal stromal tumors; familial GIST; KIT; germline mutation; GENE MUTATION; JUXTAMEMBRANE DOMAIN; ACTIVATING MUTATION; GIST; IMATINIB; NEUROFIBROMATOSIS; HYPERPIGMENTATION; PROGNOSIS;
D O I
10.3390/jpm10040234
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are characterized by activating mutations in KIT or PDGFRA genes. The vast majority of GISTs are sporadic, but rare hereditary forms have been reported, often featuring multifocality and younger age of onset. We here report the identification of a novel kindred affected by familial GIST caused by a KIT germline mutation in exon 13 (N655K). No family affected by hereditary GIST due to this KIT variant has been reported in literature so far. We were able to track the mutation in three members of the family (proband, mother, and second-degree cousin), all affected by multiple GISTs. Due to its rarity, the N655K variant is poorly characterized. We conducted in vitro drug sensitivity assays that indicated that most tyrosine kinase inhibitors (TKIs) currently included in the therapeutic armamentarium for GISTs have a limited inhibitory activity toward this mutation. However, when compared to a classical imatinib-resistant KIT mutation (T670I), N655K was slightly more sensitive to imatinib, and encouraging responses were observed with last-generation TKIs.
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页码:1 / 11
页数:11
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