The mutagenic impact of melphalan in multiple myeloma.

Abstract

The introduction of whole genome and exome sequencing partnered with advanced bioinformatic pipelines has allowed the comprehensive characterization of mutational processes (i.e., mutational signatures) in individual cancer patients. Studies focusing on multiple myeloma have defined several mutational processes, including a recently identified mutational signature (called "SBS-MM1") directly caused by exposure to high-dose melphalan (i.e., autologous stem cell transplant). High-dose melphalan exposure increases both the overall and nonsynonymous mutational burden detected between diagnosis and relapse by ~10-20%. Nevertheless, most of these mutations are acquired within the heterochromatin and late-replicating regions, rarely involving key myeloma driver genes. In this review, we summarize key studies that made this discovery possible, and we discuss potential clinical implications.

• Authors: Francesco Maura, Niels Weinhold, Benjamin Diamond, Dickran Kazandjian, Leo Rasche, Gareth Morgan, Ola Landgren
• Journal: Leukemia (Leukemia) Vol. 35 Issue 8 Pg. 2145-2150 (08 2021) ISSN: 1476-5551 [Electronic] England
• PMID: 34012133 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Mutagens
• Neoplasm Proteins
• Melphalan

Topics

• Humans
• Melphalan (adverse effects)
• Multiple Myeloma (drug therapy, genetics, pathology)
• Mutagenesis
• Mutagens (adverse effects)
• Mutation
• Neoplasm Proteins (genetics)