title: MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.
abstract: MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.
authors.affiliation: lcolomo@clinic.ub.es.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Valera
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Teresa
authors.initials: T
authors.lastname: Cardesa-Salzmann
authors.forename: Fina
authors.initials: F
authors.lastname: Climent
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.forename: Santiago
authors.initials: S
authors.lastname: Mercadal
authors.forename: Iñigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Silvana
authors.initials: S
authors.lastname: Novelli
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: José L
authors.initials: JL
authors.lastname: Mate
authors.forename: Olga
authors.initials: O
authors.lastname: Salamero
authors.forename: Juan M
authors.initials: JM
authors.lastname: Sancho
authors.forename: Leonor
authors.initials: L
authors.lastname: Arenillas
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Nadina
authors.initials: N
authors.lastname: Erill
authors.forename: Daniel
authors.initials: D
authors.lastname: Martínez
authors.forename: Paola
authors.initials: P
authors.lastname: Castillo
authors.forename: Jordina
authors.initials: J
authors.lastname: Rovira
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Luis
authors.initials: L
authors.lastname: Colomo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc