The prognosis of MYC translocation positive diffuse large B‐cell lymphoma depends on the second hit. (30th March 2015)

• Record Type: Journal Article
• Authors: Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; EI‐Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming‐Qing
• Is Part Of: Journal of pathology. Volume 1:Number 3(2015)
• Page Start: 125
• Page End: 133
• Publication Date: 2015-03-30
• Subjects: Pathology -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.07
• DOI: 10.1002/cjp2.10
• Languages: English
• ISSNs: 2056-4538

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>A proportion of <italic>MYC</italic> translocation positive diffuse large B‐cell lymphomas (DLBCL) harbour a <italic>BCL2</italic> and/or <italic>BCL6</italic> translocation, known as double‐hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with <italic>MYC</italic> translocation and form double‐hit DLBCL, and whether there is a difference in clinical outcome between the double‐hit DLBCL and those with an isolated <italic>MYC</italic> translocation. We investigated <italic>TP53</italic> gene mutations along with <italic>BCL2</italic> and <italic>BCL6</italic> translocations in a total of 234 cases of DLBCL, including 81 with <italic>MYC</italic> translocation. <italic>TP53</italic> mutations were investigated by PCR and sequencing, while <italic>BCL2</italic> and <italic>BCL6</italic> translocation was studied by interphase fluorescence in situ hybridization. The majority of <italic>MYC</italic> translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In <italic>MYC</italic> translocation positive DLBCL treated by R‐CHOP (<italic>n</italic> = 67), <italic>TP53</italic> mutation and <italic>BCL2, </italic> but not <italic>BCL6</italic> translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated <italic>MYC</italic> translocation, cases with <italic>MYC/TP53</italic> double‐hits had the worst overall survival, followed by those with <italic>MYC/BCL2</italic> double‐hits. In <italic>MYC</italic> translocation negative DLBCL treated by R‐CHOP (<italic>n</italic> = 101), <italic>TP53</italic> mutation, <italic>BCL2</italic> and <italic>BCL6</italic> translocation had no impact on patient survival. The prognosis of <italic>MYC</italic> translocation positive DLBCL critically depends on the second hit, with <italic>TP53</italic> mutations and <italic>BCL2</italic> translocation contributing to an adverse prognosis. It is pivotal to investigate both <italic>TP53</italic> mutations and <italic>BCL2</italic> translocations in <italic>MYC</italic> translocation positive DLBCL, and to distinguish double‐hit DLBCLs from those with an isolated <italic>MYC</italic> translocation.</p> </abstract>