Molecular etiology of an indolent lymphoproliferative disorder determined by whole-genome sequencing

Abstract

In an attempt to assess potential treatment options, whole-genome and transcriptome sequencing were performed on a patient with an unclassifiable small lymphoproliferative disorder. Variants from genome sequencing were prioritized using a combination of comparative variant distributions in a spectrum of lymphomas, and meta-analyses of gene expression profiling. In this patient, the molecular variants that we believe to be most relevant to the disease presentation most strongly resemble a diffuse large B-cell lymphoma (DLBCL), whereas the gene expression data are most consistent with a low-grade chronic lymphocytic leukemia (CLL). The variant of greatest interest was a predicted NOTCH2-truncating mutation, which has been recently reported in various lymphomas.

Comprehensive characterisation of intronic mis-splicing mutations in human cancers

“…1d ). Frequent loss-of-function mutations were also observed for CD58 [ 36 ] , IGLL5 [ 37 ] , IRF1 [ 38 ] , LTB [ 39 ] , MGA [ 40 ] and VMP1 [ 41 ] in blood cancers, implicating a potential tumour-suppressive role of these genes in the pathogenesis in this tissue type. Overall, these results indicate that intronic mis-splicing mutations are previously underappreciated mechanisms of cancer gene disruption.…”