INGRID QUEVEDO WANICHI
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis(2019) WANICHI, Ingrid Quevedo; MARIANI, Beatriz Marinho de Paula; FRASSETTO, Fernando Pereira; SIQUEIRA, Sheila Aparecida Coelho; MUSOLINO, Nina Rosa de Castro; CUNHA-NETO, Malebranche Berardo Carneiro; OCHMAN, Gilberto; CESCATO, Valter Angelo Sperling; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; BRONSTEIN, Marcello Delano; FRAGOSO, Maria Candida Barisson VillaresPurposeCushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.MethodsDNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n=630).ResultsWe identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p <= 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p<0.1x10(-4)). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p<0.1x10(-4)).ConclusionOur data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.