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

: Saarinen S, Kaasinen E, Karjalainen-Lindsberg ML, Vesanen K, Aavikko M, Katainen R, Taskinen M, Kytola S, Leppa S, Hietala M, Vahteristo P, Aaltonen LA

Publisher: AMER SOC HEMATOLOGY

: 2013

: Blood

: BLOOD

: 17

: 121

: 17

: 3428

: 3430

: 3

: 0006-4971

DOI: https://doi.org/10.1182/blood-2012-06-437210

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 postgerminal 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 gene. To our knowledge, this is the first time when familial clustering of PMBCL is reported. Although we propose MLL as a candidate predisposition gene for this condition, this finding needs to be validated in additional cases.