A novel genotype was identified in a patient with systemic mastocytosis (SM) and published in a case report in Cancer Genetics.

“This case provides evidence that MCL [mast cell leukemia] can have wide spectrum of genetic abnormalities as well as accumulation of mutations in various genes including BRAF,” the authors said. The study demonstrated coexistent mutations of the KIT and BRAF genes with multiple cytogenetic abnormalities in a patient with MCL, a variant of SM.

The case described a 62-year-old man from Serbia who presented with worsening dyspnea and fatigue, chest pain that appeared after exertion, and skin erythema that resolved on its own. Important previous medical history included coronary artery disease treated with stents, testicular cancer treated with bilateral orchiectomy, more than 10 tubular adenoma colon polyps without high-grade dysplasia, gastrointestinal bleeding due to multiple ulcers, hypertension, type 2 diabetes, hyperlipidemia, and peripheral arterial disease.

The patient was a former smoker for 40 years. Laboratory tests revealed a borderline white blood cell count of 4.0 K/µL and a decreased hemoglobin level and platelet count of 4.6 g/dL and 52 K/µL, respectively. Peripheral blood smear exhibited atypical cell changes consistent with MCL, and a computed tomography scan revealed splenomegaly and multiple sclerotic lesions in the bones.

Read more about SM etiology

Cytogenetic analysis of cells from a bone marrow aspirate showed 10 cells with normal karyotypes and 2 with isochromosome 6p resulting in a 6q deletion, a 6p duplication, and a 9q deletion. Genetic testing reported abnormal BRAF and KIT variants.

The patient underwent multiple treatments, including midostaurin, prednisone, cladribine, trametinib, and decitabine/venetoclax, without clinical improvement. At the 7-month follow-up, the healthcare team initiated a new therapeutic approach with avapritinib. No information on its efficacy was specified at the time of publication.

This is the first case that links a BRAF mutation with SM, let alone in concomitance with a KIT missense mutation. The complex cytogenetic alterations also constitute a rare finding in this disease since most cases of MCL have a normal cytogenetic pattern. The rarity of this genotype could be responsible for its refractory behavior to 5 different treatments. 

“The co-existence of KIT and BRAF mutations may affect the response to therapy and cause resistance,” the authors concluded.


Chen T, Malysz J, Washburn E, Songdej N, Zhang Y, Bayerl M. Mast cell leukemia with novel BRAF variant and concomitant atypical KIT variant. Cancer Genet. Published online May 24, 2022. doi:10.1016/j.cancergen.2022.05.040