Somatic Mitochondrial DNA Mutations in Diffuse Large B-Cell Lymphoma

Scientific Reports
Andy G X ZengAngela R Brooks-Wilson

Abstract

Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive hematological cancer for which mitochondrial metabolism may play an important role. Mitochondrial DNA (mtDNA) encodes crucial mitochondrial proteins, yet the relationship between mtDNA and DLBCL remains unclear. We analyzed the functional consequences and mutational spectra of mtDNA somatic mutations and private constitutional variants in 40 DLBCL tumour-normal pairs. While private constitutional variants occurred frequently in the D-Loop, somatic mutations were randomly distributed across the mitochondrial genome. Heteroplasmic constitutional variants showed a trend towards loss of heteroplasmy in the corresponding tumour regardless of whether the reference or variant allele was being lost, suggesting that these variants are selectively neutral. The mtDNA mutational spectrum showed minimal support for ROS damage and revealed strand asymmetry with increased C > T and A > G transitions on the heavy strand, consistent with a replication-associated mode of mutagenesis. These heavy strand transitions carried higher proportions of amino acid changes - which were also more pathogenic - than equivalent substitutions on the light strand. Taken together, endogenous replication-assoc...Continue Reading

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Citations

Sep 6, 2019·Cancer Research·Timothy C KennyDoris Germain

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Methods Mentioned

BETA
RNA-seq
deamination

Software Mentioned

UCSC Liftover tool
HaploGrep
MutPred
Circos
R
MitoSeek
Integrative Genome Viewer
Excel
MitoMaster
Inkscape

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