Whole Exome Sequencing of Plasma Cells Precancerosis MGUS and Malignant AL Amyloidosis Reveals Small Number of Shared Mutated Genes

Background:Immunoglobulin light chain amyloidosis (ALA) is a plasma cell dyscrasia that develops, similarly as multiple myeloma (MM), from clinically indistinguishable precancerous stage, monoclonal gammopathy of undetermined significance (MGUS). The specific mutations causing malignant transformation from MGUS to amyloidogenic immunoglobulin producing ALA are still unknown. The next generation sequencing (NGS) technology is a powerful tool that allows comprehensive description of the whole genome sequence. Previous studies have already shown highly overlapping phenotypic profile between ALA and both MGUS and MM and lack of unifying mutations in ALA patients (Paiva, 2016). Here we present whole exome NGS data of aberrant plasma cells (aPCs) obtained from patients with MGUS (n=10) and ALA (n=9). Further comparison of the exome sequences of the precancerosis and malignant stage will help to identify recurrently occurring mutations, novel oncogenic drivers and tumor suppressor genes. This will offer new prognostic markers to distinguish potential malignant plasma cell clones in MGUS that will ultimately lead to the development of fatal ALA.