title: 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 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.
authors: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors: Silva
authors: S
authors: Saarinen
authors: Eevi
authors: E
authors: Kaasinen
authors: Marja-Liisa
authors: ML
authors: Karjalainen-Lindsberg
authors: Kari
authors: K
authors: Vesanen
authors: Mervi
authors: M
authors: Aavikko
authors: Riku
authors: R
authors: Katainen
authors: Minna
authors: M
authors: Taskinen
authors: Soili
authors: S
authors: Kytölä
authors: Sirpa
authors: S
authors: Leppä
authors: Marja
authors: M
authors: Hietala
authors: Pia
authors: P
authors: Vahteristo
authors: Lauri A
authors: LA
authors: Aaltonen
mesh_terms: D000328:Adult; D059472:Exome / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics*; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010375:Pedigree
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase