The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Source, WES, and Data Analysis
2.2. Mutation Validation with Sanger Sequencing
2.3. Measurement of Plasma Levels of Inflammatory Cytokines
2.4. Genotyping for JAK2 46/1 Haplotype
3. Results
3.1. MPN Patients with SCs Are Older but Do Not Exhibit Unique Clinical Characteristics
3.2. Patterns of Genomic Variations in MPN Patients with SCs Are Not strikingly Disparate from Those of Control Cases
3.3. Genomic Alterations Are Allocated in Distinct Genes and Manifest Unique Co-Occurring Patterns in MPN with an SC
3.4. Critical Variant Replaces JAK2 as the more Prominent Disease Driver in MPN with an SC
3.5. Genomic Variants in MPN with an SC Are Enriched in Inflammation Signaling
4. Discussion
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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Variables | MPN without SC (n = 193) | MPN with SC (n = 27) | p-Value |
---|---|---|---|
Age # (mean ± SD) | 60.8 ± 16.8 | 70.2 ± 14.6 | 0.006 |
Male gender | 88 (45.6%) | 16 (59.3%) | 0.183 |
Diagnosis † | 0.774 | ||
PV | 61 | 6 | |
ET | 94 | 16 | |
PrePMF | 7 | 1 | |
PMF | 31 | 4 | |
Driver mutation | 0.448 | ||
JAK2V617F | 143 | 19 | |
JAK2 Exon 12 | 1 | 1 | |
CALR | 23 | 4 | |
MPL | 6 | 0 | |
Triple negative | 20 | 3 | |
Tumor origin | NA+ | ||
Ectoderm | - | 6 | |
Mesoderm | - | 6 | |
Endoderm | - | 14 | |
MUO ^ | - | 1 | |
Secondary MF | 21 (13%) * | 3 (13%) * | 1.000 |
Thromboembolism | 52 (26.9%) | 9 (33.3%) | 0.487 |
Major bleeding history | 31 (16.1%) | 8 (29.6%) | 0.084 |
White cell count, ×109/L | 14.88 ± 10.95 | 14.90 ± 8.11 | 0.992 |
Hemoglobin, g/dL | 14.2 ± 3.7 | 12.8 ± 3.3 | 0.062 |
Platelet, ×109/L | 619 ± 375 | 725 ± 361 | 0.172 |
Splenomegaly | 103 (58.5%) * | 12 (50%) * | 0.343 |
Coding Sequence Mutation | Amino Acid Mutation | Case Number | Cancer Type in Enrolled MPN Patients # |
---|---|---|---|
c.721_722delGGinsAA, c.745T>C |
p.Gly241Asn (G241N), p.Phe249Leu (F249L) | 3 | MUO, HCC, Pancreas |
c.745T>C | p.Phe249Leu (F249L) | 2 | Lung, Lung |
c.745T>C, c.721_722insAGAGA, c.716_717insAAGACAGAAGACAGACACACACAGTGAGAGAGACAGA | p.Phe249Leu (F249L), p.Gly241fs *29, p.Gly241fs *25 | 1 | HCC |
c.721_722delGGinsAA | p.Gly241Asn (G241N) | 1 | Lung |
c.418G>A | p.Val140Ile (V140I) | 1 | Cervix |
Coding Sequence Mutation | Amino Acid Mutation | COSMIC | FATHMM Prediction | Cancer Type in COSMIC |
---|---|---|---|---|
c.745T>C | p.Phe249Leu (F249L) | COSM1739982 |
Pathogenic (score 0.86) |
14 Carcinoma, 1 Lymphoma |
c.418G>A | p.Val140Ile (V140I) | COSM1239293 |
Neutral (score 0.09) |
4 Carcinoma, 1 Lymphoma |
c.721_722delGGinsAA | p.Gly241Asn (G241N) | Not found | ||
c.721_722insAGAGA | p.Gly241fs *29 | Not found | ||
c.716_717insAAGACAGAAGACAGACACACACAGTGAGAGAGACAGA | p.Gly241fs *25 | Not found |
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Hsu, C.-C.; Wang, Y.-H.; Chen, Y.-Y.; Chen, Y.-J.; Lu, C.-H.; Wu, Y.-Y.; Yang, Y.-R.; Tsou, H.-Y.; Li, C.-P.; Huang, C.-E.; et al. The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers. Cancers 2022, 14, 3435. https://doi.org/10.3390/cancers14143435
Hsu C-C, Wang Y-H, Chen Y-Y, Chen Y-J, Lu C-H, Wu Y-Y, Yang Y-R, Tsou H-Y, Li C-P, Huang C-E, et al. The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers. Cancers. 2022; 14(14):3435. https://doi.org/10.3390/cancers14143435
Chicago/Turabian StyleHsu, Chia-Chen, Ying-Hsuan Wang, Yi-Yang Chen, Ying-Ju Chen, Chang-Hsien Lu, Yu-Ying Wu, Yao-Ren Yang, Hsing-Yi Tsou, Chian-Pei Li, Cih-En Huang, and et al. 2022. "The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers" Cancers 14, no. 14: 3435. https://doi.org/10.3390/cancers14143435