Primary mediastinal large B-cell lymphoma segregating in a family: Exome sequencing identifies MLL as a candidate predisposition gene

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) accounting for 2% to 4% of all non-Hodgkin lymphomas. We report a family of 3 siblings with PMBCL and their cousin with extranodal DLBCL. The histopathological characteristics of lymphomas of all 4 patients are similar, implying post–germinal center differentiation and growth deregulation by other mechanisms than BCL2-mediated inhibition of apoptosis and suggesting a shared biological background. We aimed to identify the genetic defect underlying lymphoma susceptibility in this family using exome sequencing and linkage analysis. The only variant segregating in all 4 patients and not reported in genetic databases was 5533C>A (His1845Asn) in the MLL ene To our knowled e this is the first time when familial clusterin of PMBCL is re orted , Although we propose MLL as a candidate predisposition gene for this condition, this finding needs to be validated in additional cases.