RESUMO
The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n=46, gain n=23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36-0.93, P=0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies.
Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histona-Lisina N-Metiltransferase/genética , Linfoma Folicular/genética , Adulto , Idoso , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Histona Metiltransferases , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Metilação/efeitos dos fármacos , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de RNARESUMO
A case of intestinal gas explosion during the course of carcinologic surgery in a 51-year-old patient is reported. This accident, often dramatic, has become exceptional since the use of mannitol for colonic preparation has disappeared. This incident occurred during the course of a total pelvic exenteration performed under general anaesthesia with inhalation of both a mixture oxygen-nitrous oxide and volatile agents. The colon incision with an electrocautery was contemporaneous with a violent deflagration accountable for organic lesions. This case report reminds us that the risk of a dangerous explosion persists in relation with surgical, anaesthetic and individual risk factors.