Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study

Lorenz Oelschläger; Axel Künstner; Friederike Frey; Theo Leitner; Lisa Leypoldt; Niklas Reimer; Niklas Gebauer; Lorenz Bastian; Katja Weisel; Verena Wilbeth Sailer; Christoph Röcken; Wolfram Klapper; Björn Konukiewitz; Eva Maria Murga Penas; Michael Forster; Natalie Schub; Helal M.M. Ahmed; Jutta Kirfel; Nikolas Christian Cornelius von Bubnoff; Hauke Busch; Cyrus Khandanpour

doi:10.3390/ijms252413418

Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study

Lorenz Oelschläger, Axel Künstner, Friederike Frey, Theo Leitner, Lisa Leypoldt, Niklas Reimer, Niklas Gebauer, Lorenz Bastian, Katja Weisel, Verena Wilbeth Sailer, Christoph Röcken, Wolfram Klapper, Björn Konukiewitz, Eva Maria Murga Penas, Michael Forster, Natalie Schub, Helal M.M. Ahmed, Jutta Kirfel, Nikolas Christian Cornelius von Bubnoff, Hauke BuschCyrus Khandanpour^*

^*Corresponding author for this work

Abstract

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.

Original language	English
Article number	13418
Journal	International Journal of Molecular Sciences
Volume	25
Issue number	24
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms252413418
Publication status	Published - 12.2024

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)
Research Area: Medical Genetics

DFG Research Classification Scheme

2.22-14 Hematology, Oncology
2.11-05 General Genetics and Functional Genome Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms252413418

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Oelschläger, L., Künstner, A., Frey, F., Leitner, T., Leypoldt, L., Reimer, N., Gebauer, N., Bastian, L., Weisel, K., Sailer, V. W., Röcken, C., Klapper, W., Konukiewitz, B., Murga Penas, E. M., Forster, M., Schub, N., Ahmed, H. M. M., Kirfel, J., von Bubnoff, N. C. C., ... Khandanpour, C. (2024). Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study. International Journal of Molecular Sciences, 25(24), Article 13418. https://doi.org/10.3390/ijms252413418

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title = "Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study",

abstract = "The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.",

author = "Lorenz Oelschl{\"a}ger and Axel K{\"u}nstner and Friederike Frey and Theo Leitner and Lisa Leypoldt and Niklas Reimer and Niklas Gebauer and Lorenz Bastian and Katja Weisel and Sailer, {Verena Wilbeth} and Christoph R{\"o}cken and Wolfram Klapper and Bj{\"o}rn Konukiewitz and {Murga Penas}, {Eva Maria} and Michael Forster and Natalie Schub and Ahmed, {Helal M.M.} and Jutta Kirfel and {von Bubnoff}, {Nikolas Christian Cornelius} and Hauke Busch and Cyrus Khandanpour",

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year = "2024",

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language = "English",

volume = "25",

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Oelschläger, L , Künstner, A, Frey, F, Leitner, T, Leypoldt, L, Reimer, N , Gebauer, N, Bastian, L, Weisel, K, Sailer, VW, Röcken, C, Klapper, W, Konukiewitz, B, Murga Penas, EM, Forster, M, Schub, N, Ahmed, HMM , Kirfel, J , von Bubnoff, NCC , Busch, H & Khandanpour, C 2024, 'Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study', International Journal of Molecular Sciences, vol. 25, no. 24, 13418. https://doi.org/10.3390/ijms252413418

TY - JOUR

T1 - Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study

AU - Oelschläger, Lorenz

AU - Künstner, Axel

AU - Frey, Friederike

AU - Leitner, Theo

AU - Leypoldt, Lisa

AU - Reimer, Niklas

AU - Gebauer, Niklas

AU - Bastian, Lorenz

AU - Weisel, Katja

AU - Sailer, Verena Wilbeth

AU - Röcken, Christoph

AU - Klapper, Wolfram

AU - Konukiewitz, Björn

AU - Murga Penas, Eva Maria

AU - Forster, Michael

AU - Schub, Natalie

AU - Ahmed, Helal M.M.

AU - Kirfel, Jutta

AU - von Bubnoff, Nikolas Christian Cornelius

AU - Busch, Hauke

AU - Khandanpour, Cyrus

PY - 2024/12

Y1 - 2024/12

N2 - The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.

AB - The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.

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U2 - 10.3390/ijms252413418

DO - 10.3390/ijms252413418

M3 - Journal articles

C2 - 39769182

AN - SCOPUS:85215107149

SN - 1661-6596

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 24

M1 - 13418

ER -

Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma—A Pilot Study

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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