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Multiple myeloma gammopathies

Genetic predisposition for multiple myeloma

Subjects

Abstract

Multiple myeloma (MM) is the second most common blood malignancy. Epidemiological family studies going back to the 1920s have provided evidence for familial aggregation, suggesting a subset of cases have an inherited genetic background. Recently, studies aimed at explaining this phenomenon have begun to provide direct evidence for genetic predisposition to MM. Genome-wide association studies have identified common risk alleles at 24 independent loci. Sequencing studies of familial cases and kindreds have begun to identify promising candidate genes where variants with strong effects on MM risk might reside. Finally, functional studies are starting to give insight into how identified risk alleles promote the development of MM. Here, we review recent findings in MM predisposition field, and highlight open questions and future directions.

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Fig. 1: Genomic location of MM risk alleles identified in genome-wide association studies.

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Acknowledgements

The authors were supported by Knut and Alice Wallenberg’s Foundation (2012.0193 and 2017.0436), the Swedish Research Council (2018-00424), the Swedish Cancer Society (2017/265), the Nordic Cancer Union (R217-A13329), and the Stiftelsen Borås forsknings- och utvecklingsfond mot cancer. RSH is supported by BLOODWISE and MYELOMA UK.

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Pertesi, M., Went, M., Hansson, M. et al. Genetic predisposition for multiple myeloma. Leukemia 34, 697–708 (2020). https://doi.org/10.1038/s41375-019-0703-6

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