Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Patients with MM (n = 97) |
---|---|
Age, years, median and range | 55 (29–83) |
Males/females | 43/54 |
Type of secretion | |
G | 59 (61%) |
A | 19 (20%) |
BJ | 15 (15%) |
D | 4 (4%) |
Type of FLC | |
κ | 58 (60%) |
λ | 39 (40%) |
D-S stage | |
IA | 5 (5%) |
IB | 2 (2%) |
IIA | 16 (17%) |
IIIA | 58 (60%) |
IIIB | 15 (15%) |
Not available | 1 (1%) |
ISS stage | |
I | 29 (30%) |
II | 20 (21%) |
III | 17(17%) |
Not available | 31 (32%) |
Hemoglobin (g/L), median and range | 109 (66–156) |
LDH (U/L), median and range | 170 (65–694) |
% plasma cells in bone marrow aspiration, median and range | 16 (2.4–92) |
FISH | |
Standard risk | 45 (46%) |
High risk | 49 (51%) |
Not available | 3 (3%) |
Plasmacytomas | |
Yes | 57 (59%) |
No | 40 (41%) |
n = 57 | |
bone | 51 (90%) |
extramedullary | 2 (3%) |
bone and extramedullary | 4 (7%) |
# | Mutations in CD138+ Bone Marrow Cells | Mutations in ctDNA | Disease Features |
---|---|---|---|
1 | none | KRAS c.286 delT | High LDH; ISS stage III; double-HIT: del17p13, 1q21; amyloidosis; Relapse/refractory |
2 | none | NRAS L95P | 1q21; only partial remission after HSCT |
3 | none | KRAS G12V | High LDH; 1q21; relapse/refractory |
4 | KRAS G12S | KRASV29A | T (4;14); only partial remission after 2 rounds of HSCT |
5 | NRAS Y64N | none | Plasma cell leukemia; high LDH; 1q21; extramedullary plasmacytomas; D-myeloma; death in induction |
6 | KRAS A59G | none | only partial remission after HSCT |
7 | KRAS L19F | none | ISS stage III; double HIT: t(14;16), 1q21; relapse/refractory; death in induction |
# | LOH Loci in Bone Marrow | Mutations in Bone Marrow | LOH Loci in ctDNA | Mutations in ctDNA | DNA Concentration (ng/mL) |
---|---|---|---|---|---|
1 | 2 | KRAS | 0 | none | 17.5 |
2 | 2 | BRAF | 0 | none | 11 |
3 | 6 | 2 KRAS | 0 | none | 22 |
4 | 0 | NRAS | 0 | none | 13.5 |
5 | 2 | KRAS | 0 | none | 17 |
6 | 0 | - | 3 | KRAS | 45.75 |
7 | 3 | KRAS | 4 (shared 1) | none | 46.5 |
8 | 0 | KRAS | 6 | none | 32 |
9 | 8 | NRAS | 7 (shared 2) | none | 8 |
10 | 0 | KRAS | 1 | none | 10 |
11 | 0 | NRAS | 1 | none | 17 |
12 | 2 | KRAS | 5 (shared 1) | none | 20 |
13 | 2 | - | 3 (shared 1) | NRAS | 77 |
14 | 5 | KRAS G12S | 3 (shared 2) | KRAS V29A | 17 |
15 | 2 | BRAF | 4 (shared none) | none | 30 |
16 | 6 | NRAS BRAF | 3 (shared 2) | none | 17 |
17 | 0 | - | 4 | KRAS | 50 |
18 | 5 | NRAS | 2 (shared none) | none | 5 |
19 | 1 | BRAF | 1 (shared none) | none | 10 |
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Soloveva, M.; Solovev, M.; Risinskaya, N.; Nikulina, E.; Yakutik, I.; Biderman, B.; Obukhova, T.; Chabaeva, Y.; Kulikov, S.; Sudarikov, A.; et al. Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma. Int. J. Mol. Sci. 2024, 25, 9426. https://doi.org/10.3390/ijms25179426
Soloveva M, Solovev M, Risinskaya N, Nikulina E, Yakutik I, Biderman B, Obukhova T, Chabaeva Y, Kulikov S, Sudarikov A, et al. Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma. International Journal of Molecular Sciences. 2024; 25(17):9426. https://doi.org/10.3390/ijms25179426
Chicago/Turabian StyleSoloveva, Maiia, Maksim Solovev, Natalya Risinskaya, Elena Nikulina, Igor Yakutik, Bella Biderman, Tatiana Obukhova, Yulia Chabaeva, Sergej Kulikov, Andrey Sudarikov, and et al. 2024. "Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma" International Journal of Molecular Sciences 25, no. 17: 9426. https://doi.org/10.3390/ijms25179426