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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Multiple Myeloma*/genetics ; Exome Sequencing*/methods ; Mutation*; Humans ; Pilot Projects ; Female ; Male ; Middle Aged ; Prognosis ; Aged ; DNA Mutational Analysis/methods ; Adult

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.

Clin Lymphoma Myeloma Leuk. 2020 Feb;20(2):57-62. (PMID: 31734019)
Leukemia. 2024 May;38(5):1172-1177. (PMID: 38461190)
Nat Commun. 2021 Mar 25;12(1):1861. (PMID: 33767199)
Blood. 2011 Dec 8;118(24):6368-79. (PMID: 21917757)
Lancet Haematol. 2022 Sep;9(9):e670-e677. (PMID: 35843248)
Nature. 2011 Mar 24;471(7339):467-72. (PMID: 21430775)
MedComm (2020). 2022 Jun 02;3(2):e146. (PMID: 35665368)
Leukemia. 2018 Jul;32(7):1561-1566. (PMID: 29467487)
Geroscience. 2023 Apr;45(2):727-746. (PMID: 36508077)
Haematologica. 2022 Aug 01;107(8):1891-1901. (PMID: 35045690)
Cold Spring Harb Perspect Med. 2017 Mar 1;7(3):. (PMID: 28062559)
Cells. 2021 Feb 05;10(2):. (PMID: 33562668)
J Oncol. 2022 Apr 5;2022:2800488. (PMID: 35422863)
Nature. 2013 Jul 11;499(7457):214-218. (PMID: 23770567)
Leukemia. 2008 Dec;22(12):2280-4. (PMID: 18528420)
JCO Oncol Pract. 2020 Jan;16(1):5-14. (PMID: 32039665)
Int J Mol Sci. 2020 Sep 14;21(18):. (PMID: 32937821)
Blood Cancer J. 2020 Aug 11;10(8):82. (PMID: 32782240)
Blood. 2018 Aug 9;132(6):587-597. (PMID: 29884741)
Nat Commun. 2020 Apr 21;11(1):1917. (PMID: 32317634)
Nat Immunol. 2022 Dec;23(12):1763-1776. (PMID: 36316474)
Blood. 2016 Sep 1;128(9):1226-33. (PMID: 27458004)
Blood. 2009 May 28;113(22):5412-7. (PMID: 19179464)
Semin Hematol. 2011 Jan;48(1):4-12. (PMID: 21232653)
J Cancer Metastasis Treat. 2021;7:. (PMID: 34778567)
Oncotarget. 2015 Sep 29;6(29):26826-40. (PMID: 26308486)
Trends Mol Med. 2019 Oct;25(10):853-865. (PMID: 31248782)
F1000Res. 2020 Jan 29;9:63. (PMID: 32269765)
J Clin Oncol. 2020 Sep 20;38(27):3107-3118. (PMID: 32687451)
Sci Rep. 2017 Nov 21;7(1):15928. (PMID: 29162920)
Nat Biotechnol. 2013 Mar;31(3):213-9. (PMID: 23396013)
Genome Res. 2018 Nov;28(11):1747-1756. (PMID: 30341162)
Br J Haematol. 2014 Aug;166(4):529-39. (PMID: 24766330)
Oncogenesis. 2018 Jun 18;7(6):48. (PMID: 29910466)
Nat Commun. 2019 Jul 5;10(1):2969. (PMID: 31278357)
Genome Biol. 2016 Jun 06;17(1):122. (PMID: 27268795)
Genome Res. 2010 Sep;20(9):1297-303. (PMID: 20644199)
Cancer Res. 2017 Sep 15;77(18):4755-4762. (PMID: 28904067)
J Clin Oncol. 2024 Apr 10;42(11):1229-1240. (PMID: 38194610)
Oncogene. 2022 Oct;41(41):4573-4590. (PMID: 36050467)
Science. 2013 Mar 29;339(6127):1546-58. (PMID: 23539594)
Lancet Oncol. 2014 Nov;15(12):e538-48. (PMID: 25439696)
Blood. 2009 May 28;113(22):5418-22. (PMID: 19234139)
Am J Hematol. 2022 Aug;97(8):1086-1107. (PMID: 35560063)
Blood. 2021 Nov 4;138(18):1705-1720. (PMID: 34077955)
Cancers (Basel). 2021 Jan 09;13(2):. (PMID: 33435306)
Nat Biotechnol. 2020 Mar;38(3):276-278. (PMID: 32055031)
Bioinformatics. 2018 Sep 1;34(17):i884-i890. (PMID: 30423086)
Nat Commun. 2015 Apr 23;6:6997. (PMID: 25904160)
Commun Biol. 2021 Mar 29;4(1):424. (PMID: 33782531)
Epidemiology. 2023 Sep 1;34(5):652-660. (PMID: 37462467)
Cancers (Basel). 2021 Mar 19;13(6):. (PMID: 33808654)
Cell. 2007 Jun 29;129(7):1311-23. (PMID: 17604720)
J Hematol Oncol. 2018 May 18;11(1):67. (PMID: 29776381)
BMC Med Genomics. 2014 Dec 03;7:64. (PMID: 25466818)
Br J Haematol. 2017 Nov;179(3):421-429. (PMID: 28771672)
Nat Commun. 2016 Jan 05;7:10258. (PMID: 26728187)
Nature. 2020 Feb;578(7793):94-101. (PMID: 32025018)
Cancers (Basel). 2017 Mar 28;9(4):. (PMID: 28350342)
Leuk Lymphoma. 2018 Nov;59(11):2524-2534. (PMID: 29322846)
Cancer Cell. 2014 Jan 13;25(1):91-101. (PMID: 24434212)
Nat Commun. 2023 Mar 9;14(1):1290. (PMID: 36894562)
Br J Haematol. 2021 Oct;195(2):283-286. (PMID: 34244996)
Nat Commun. 2017 Aug 16;8(1):268. (PMID: 28814763)
Nat Commun. 2014;5:2997. (PMID: 24429703)
Front Oncol. 2021 Oct 04;11:745187. (PMID: 34671561)
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894. (PMID: 30371827)
J Exp Clin Cancer Res. 2018 May 9;37(1):101. (PMID: 29743091)
Br J Haematol. 2014 Apr;165(1):89-101. (PMID: 24405121)
Cancers (Basel). 2023 Jul 01;15(13):. (PMID: 37444566)
J Clin Oncol. 2015 Nov 20;33(33):3911-20. (PMID: 26282654)
Leukemia. 2018 Apr;32(4):1044-1048. (PMID: 29209044)
Leukemia. 2018 Dec;32(12):2604-2616. (PMID: 29789651)
DNA Repair (Amst). 2020 Nov;95:102948. (PMID: 32866776)
Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20785-20793. (PMID: 32778592)
Br J Cancer. 2020 Mar;122(7):943-952. (PMID: 32042067)
Cell. 2012 Nov 21;151(5):937-50. (PMID: 23178117)
Leukemia. 2022 Jul;36(7):1887-1897. (PMID: 35643867)
Nat Commun. 2015 Dec 07;6:8866. (PMID: 26638776)
Nat Rev Clin Oncol. 2017 Feb;14(2):100-113. (PMID: 27531699)
Annu Rev Biochem. 2016 Jun 2;85:485-514. (PMID: 27145839)
J Clin Oncol. 2015 Sep 10;33(26):2863-9. (PMID: 26240224)
Blood Adv. 2022 Jan 25;6(2):368-372. (PMID: 34500459)
Blood. 2015 May 14;125(20):3069-75. (PMID: 25838344)

FKZ01KD2103A Federal Ministry of Education and Research

Keywords: multiple myeloma; somatic signatures; whole-exome sequencing

Date Created: 20250108 Date Completed: 20250108 Latest Revision: 20250108

20250110

PMC11680055

10.3390/ijms252413418

39769182