Prevalence of Cytoplasmic Actin Mutations in Diffuse Large B-Cell Lymphoma and Multiple Myeloma: A Functional Assessment Based on Actin Three-Dimensional Structures.

Laura Witjes,Marleen Van Troys,Bruno Verhasselt,Christophe Ampe

doi:10.3390/ijms21093093

Laura Witjes, Marleen Van Troys + Show 2 more

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https://doi.org/10.3390/ijms21093093

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Abstract

Mutations in actins have been linked to several developmental diseases. Their occurrence across different cancers has, however, not been investigated. Using the cBioPortal database we show that human actins are infrequently mutated in patient samples of various cancers types. Nevertheless, ranking these studies by mutational frequency suggest that some have a higher percentage of patients with ACTB and ACTG1 mutations. Within studies on hematological cancers, mutations in ACTB and ACTG1 are associated with lymphoid cancers since none have currently been reported in myeloid cancers. Within the different types of lymphoid cancers ACTB mutations are most frequent in diffuse large B-cell lymphoma (DLBCL) and ACTG1 mutations in multiple myeloma. We mapped the ACTB and ACTG1 mutations found in these two cancer types on the 3D-structure of actin showing they are in regions important for actin polymer formation or binding to myosin. The potential effects of the mutations on actin properties imply that mutations in cytoplasmic actins deserve dedicated research in DLBCL and multiple myeloma.

Highlights

Actins form a highly conserved family of proteins [1,2]
If the two cytoplasmic actin genes ACTB and ACTG1 are more frequently mutated in hematological malignancies than sequencing screens suggest [12,13,14,15,16,17], this should be apparent from a comparison of the alteration frequency of these two genes in blood cancers relative to other cancer types
Using patient data available at cBioPortal we show that mutations in ACTB and ACTG1 in hematological cancers all occur in lymphoid cancers

Summary

Introduction

Actins form a highly conserved family of proteins [1,2]. These proteins form the central building blocks of the actin cytoskeleton which is involved in muscle contraction, cell division, adhesion and migration. In three independent studies on multiple myeloma, ACTG1 was identified as one of the most frequently mutated genes in this hematological cancer involving plasma cells [13,14,15] and it even met the criteria for potentially being a candidate driver gene in multiple myeloma. These studies did not compare actin mutations relative to other cancers (including other hematological cancers) nor were the mutations considered or interpreted structurally

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