Molecular Profiling of Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma and Cutaneous Melanoma
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients’ Samples
2.2. Histology and Immunohistochemistry
2.3. DNA Isolation
2.4. Merkel Cell Polyomavirus Molecular Detection
2.5. BRAF StripAssay
2.6. Next-Generation Sequencing
3. Results
3.1. Clinical Presentations
3.2. Histological Features Including Immunohistochemistry
3.3. Merkel Cell Polyomavirus Detection
3.4. Merkel Cell Polyomavirus Amplification in Melanoma Samples
3.5. NGS-Based Mutation Profiling
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient | Gender | Age (years) | Location | Size (cm) | Depth (cm) | Treatment | Metastasis | Survival (Month) |
---|---|---|---|---|---|---|---|---|
1 | M | 89 | left knee | 4 | 1 | excision and chemotherapy | n.a. | 7 |
2 | M | 80 | right face | 1.5 | 0.9 | excision | lost follow-up | |
3 | M | 88 | right chest | 2.2 | 0.5 | excision | lost follow-up | |
4 | F | 68 | left shoulder | 1.1 | 0.7 | neoadjuvant chemotherapy | axillary lymph node | 24 |
5 | M | 83 | right thigh | 2.4 | 2.2 | excision | lost follow-up | |
6 | M | 76 | right 3rd finger | 1 | 6.7 | excision | n.a. | 9 |
7 | F | 85 | right face | 1.4 | 1.6 | radiotherapy | lost follow-up | |
8 | F | 63 | right gluteus | 2 | 0.4 | radiotherapy | n.a. | 6 |
9 | M | 68 | right forearm | 6 | 1 | excision | lymp node | 3 |
Cases | Lymphocyte Infiltration | Ki-67 (%) | Cytokeratin 20 | Synaptophysin | Chromogranin A | Thyroid Transcription Factor 1 | p53 | MCPyV IHC | LT1 PCR | LT3 PCR | VP1 PCR |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | low | 60 | + | + | + | - | diffuse + | + | - | + | + |
2 | low | 60 | + | + | + | - | patchy + | + | - | + | + |
3 | low | 50 | + | + | - | - | diffuse + | - | - | - | + |
4 | low | 60 | dot-like | marked | marked | - | - | diffuse + | - | + | - |
5 | low | 80 | dot-like | marked | focal | - | weakly + | - | - | - | - |
6 | moderate | 70 | dot-like | marked | marked | - | - | patchy + | - | + | - |
7 | low | 60 | dot-like | dot-like | dot-like | - | - | - | - | - | - |
8 | moderate | 70 | dot-like | + | patchy + | - | diffuse + | - | - | + | - |
9 | low | 60 | dot-like | dot-like | dot like | - | patchy + | diffuse + | - | + | + |
Scheme | Gene Symbol | Gene Name | Nucleotide Change | Amino Acid Change | Variant Allele Frequency (%) | Clinical Sgnificance | COSMIC ID |
---|---|---|---|---|---|---|---|
S1 (+) | RB1 | retinoblastoma 1 | c.2033A>T | p.His678Leu | 48 | no data available | - |
S2 (+) | STK11 | serine/threonine kinase 11 | c.1062C>G | p.Phe354Leu | 54.55 | neutral | COSM21360 |
S3 (+) | EGFR | epidermal growth factor receptor | c.2137G>A | p.Glu713Lys | 30.25 | no data available | - |
FBXW7 | F-box/WD repeat-containing protein 7 | c.1031C>T | p.Ser344Phe | 89.3 | COSM1177864 | ||
TP53 | tumor protein P53 | c.832C>T | p.Pro278Ser | 92.4 | pathogenic | COSM10939 | |
S4 (+) | CTNNB1 | catenin beta-1 | c.59C>T | p.Ala20Val | 9 | pathogenic | COSM5702 |
S5 (-) | CDKN2A | cyclin-dependent kinase inhibitor 2A | c.442G>A | p.Ala148Thr | 50 | neutral | COSM3774362 |
FGFR1 | fibroblast growth factor receptor 1 | c.2181-6C>T | - | 48.6 | no data available | - | |
S6 (+) | ABL1 | tyrosine-protein kinase ABL1 | c.740A>G | p.Lys247Arg | 42.1 | benign | - |
FOXL2 | forkhead box protein L2 | c.536C>G | p.Ala179Gly | 65.3 | benign | COSM4600643 | |
HNF1A | hepatocyte nuclear factor 1 A | c.864del | p.Pro291GlnfsTer51 | 7.5 | pathogenic | COSM935974 | |
S7 (-) | no mutation detected | ||||||
S8 (+) | JAK3 | Janus kinase 3 | c.2164G>A | p.Val722Ile | 42.5 | neutral | COSM34213 |
S9 (+) | TP53 | tumor protein P53 | c.-28-4G>A | - | 4.5 | no data available | - |
M1 (+) | BRAF | serine/threonine kinase BRAF | c.1799_1800delinsAA | p.Val600Glu | 40 | pathogenic | COSM475 |
PIK3CA | phosphatidylinositol bisphosphate 3-kinase | c.1031T>C | p.Val344Ala | 13.4 | pathogenic | COSM86951 | |
STK11 | serine/threonine kinase 11 | c.1211C>T | p.Ser404Phe | 35.1 | no data available | - | |
M2 (+) | BRAF | serine/threonine kinase BRAF | c.1799T>A | p.Val600Glu | 22.2 | pathogenic | COSM476 |
CDKN2A | cyclin-dependent kinase inhibitor 2A | c.169dup | p.Ala57GlyfsTer63 | 20.6 | pathogenic | COSM110662 | |
SMAD4 | mothers against decapentaplegic homolog 4 | c.122A>G | p.Glu41Gly | 5.7 | no data available | - | |
M3 (+) | BRAF | serine/threonine kinase BRAF | c.1799T>A | p.Val600Glu | 15.4 | pathogenic | COSM476 |
APC | adenomatous polyposis coli | c.3949G>C | p.Glu1317Gln | 50 | pathogenic | COSM19099 |
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Mokánszki, A.; Méhes, G.; Csoma, S.L.; Kollár, S.; Chang Chien, Y.-C. Molecular Profiling of Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma and Cutaneous Melanoma. Diagnostics 2021, 11, 212. https://doi.org/10.3390/diagnostics11020212
Mokánszki A, Méhes G, Csoma SL, Kollár S, Chang Chien Y-C. Molecular Profiling of Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma and Cutaneous Melanoma. Diagnostics. 2021; 11(2):212. https://doi.org/10.3390/diagnostics11020212
Chicago/Turabian StyleMokánszki, Attila, Gábor Méhes, Szilvia Lilla Csoma, Sándor Kollár, and Yi-Che Chang Chien. 2021. "Molecular Profiling of Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma and Cutaneous Melanoma" Diagnostics 11, no. 2: 212. https://doi.org/10.3390/diagnostics11020212
APA StyleMokánszki, A., Méhes, G., Csoma, S. L., Kollár, S., & Chang Chien, Y.-C. (2021). Molecular Profiling of Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma and Cutaneous Melanoma. Diagnostics, 11(2), 212. https://doi.org/10.3390/diagnostics11020212