title: The prognosis ofMYCtranslocation positive diffuse large B-cell lymphoma depends on the second hit.
abstract: A proportion ofMYCtranslocation positive diffuse large B-cell lymphomas (DLBCL) harbour aBCL2and/orBCL6translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate withMYCtranslocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolatedMYCtranslocation. We investigatedTP53gene mutations along withBCL2andBCL6translocations in a total of 234 cases of DLBCL, including 81 withMYCtranslocation.TP53mutations were investigated by PCR and sequencing, whileBCL2andBCL6translocation was studied by interphase fluorescence in situ hybridization. The majority ofMYCtranslocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. InMYCtranslocation positive DLBCL treated by R-CHOP (n= 67),TP53mutation andBCL2,but notBCL6translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolatedMYCtranslocation, cases withMYC/TP53double-hits had the worst overall survival, followed by those withMYC/BCL2double-hits. InMYCtranslocation negative DLBCL treated by R-CHOP (n= 101),TP53mutation,BCL2andBCL6translocation had no impact on patient survival. The prognosis ofMYCtranslocation positive DLBCL critically depends on the second hit, withTP53mutations andBCL2translocation contributing to an adverse prognosis. It is pivotal to investigate bothTP53mutations andBCL2translocations inMYCtranslocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolatedMYCtranslocation.
authors.affiliation: Division of Molecular Histopathology Department of Pathology University of Cambridge UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Clipson
authors.affiliation: Haematological Malignancy Diagnostic Service St. James's Institute of Oncology Leeds UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Barrans
authors.affiliation: Division of Molecular Histopathology Department of Pathology University of Cambridge UK.
authors.forename: Naiyan
authors.initials: N
authors.lastname: Zeng
authors.affiliation: Department of Health Sciences Epidemiology and Cancer Statistics Group University of York York UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Crouch
authors.affiliation: Division of Molecular HistopathologyDepartment of PathologyUniversity of CambridgeUK; Department of HaematologyAddenbrooke's Hospital, Cambridge University Hospitals NHS Foundation TrustCambridgeUK.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Grigoropoulos
authors.affiliation: Department of Histopathology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division of Molecular Histopathology Department of Pathology University of Cambridge UK.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kocialkowski
authors.affiliation: Division of Molecular Histopathology Department of Pathology University of Cambridge UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of Molecular Histopathology Department of Pathology University of Cambridge UK.
authors.forename: Yuanxue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Haematological Malignancy Diagnostic Service St. James's Institute of Oncology Leeds UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Worrillow
authors.affiliation: Department of Pathology Western General Hospital Edinburgh UK.
authors.forename: John
authors.initials: J
authors.lastname: Goodlad
authors.affiliation: Department of Haematology Western General Hospital Edinburgh UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Buxton
authors.affiliation: Department of Haematology and Department of Cytogenetics GSTS Pathology Guy's and St. Thomas NHS Foundation Trust London UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Neat
authors.affiliation: Department of Haematology GSST Kings Health Partners London UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Fields
authors.affiliation: Histopathology Department St Thomas' Hospital and King's College London UK.
authors.forename: Bridget
authors.initials: B
authors.lastname: Wilkins
authors.affiliation: Department of Histopathology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Grant
authors.affiliation: Department of Histopathology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Wright
authors.affiliation: Department of Haematology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: Hesham
authors.initials: H
authors.lastname: Ei-Daly
authors.affiliation: Department of Haematology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: George A
authors.initials: GA
authors.lastname: Follows
authors.affiliation: Department of Health Sciences Epidemiology and Cancer Statistics Group University of York York UK.
authors.forename: Eve
authors.initials: E
authors.lastname: Roman
authors.affiliation: Department of Haematology Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge UK.
authors.forename: A James
authors.initials: AJ
authors.lastname: Watkins
authors.affiliation: Cancer Research UK Centre University of Southampton Southampton United Kingdom.
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Johnson
authors.affiliation: Haematological Malignancy Diagnostic Service St. James's Institute of Oncology Leeds UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jack
authors.affiliation: Division of Molecular HistopathologyDepartment of PathologyUniversity of CambridgeUK; Department of HistopathologyAddenbrooke's Hospital, Cambridge University Hospitals NHS Foundation TrustCambridgeUK.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
keywords: DLBCL; TP53 mutation; chromosome translocation; double‐hit; overall survival