Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma
Here, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of the <i>BRAF&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/21/5141 |
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| author | Szilvia Lilla Csoma Kristóf Madarász Yi Che Chang Chien Gabriella Emri Judit Bedekovics Gábor Méhes Attila Mokánszki |
| author_facet | Szilvia Lilla Csoma Kristóf Madarász Yi Che Chang Chien Gabriella Emri Judit Bedekovics Gábor Méhes Attila Mokánszki |
| author_sort | Szilvia Lilla Csoma |
| collection | DOAJ |
| description | Here, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of the <i>BRAF</i> p.V600E somatic pathogenic variant. In the prospective study, a total of 68 plasma and paired tdDNA samples, and in the retrospective cohort, a total of 100 tdDNA samples were analyzed using dPCR and reverse hybridization StripAssay. The Breslow depth (BD) and Clark level were applied to categorize the study population. Our results demonstrate that dPCR is a highly sensitive and specific method for the detection of <i>BRAF</i> p.V600E somatic variants in cfDNA samples from PCM patients. A strong correlation was detected between BD and cfDNA concentration in all mutant and negative cases, between the tdDNA concentration and the tumor-derived variant allele frequency (VAF) of <i>BRAF</i> p.V600E, between the tdVAF and the cfVAF in all cases, and between the cfDNA and cfVAF in mutant cases. The tdVAF and cfVAF of <i>BRAF</i> p.V600E and cfDNA concentration were the highest in Clark’s V category. The cfDNA concentration was statistically significantly higher in Clark’s III, IV, and V groups compared to cases with a better prognosis. It can also be explained by the fact that cases with a more advanced stage classification release more cfDNA into the peripheral circulation. |
| first_indexed | 2024-03-11T11:32:30Z |
| format | Article |
| id | doaj.art-4667062574124c399334c6bf14456da0 |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T11:32:30Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4667062574124c399334c6bf14456da02023-11-10T15:00:00ZengMDPI AGCancers2072-66942023-10-011521514110.3390/cancers15215141Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous MelanomaSzilvia Lilla Csoma0Kristóf Madarász1Yi Che Chang Chien2Gabriella Emri3Judit Bedekovics4Gábor Méhes5Attila Mokánszki6Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Dermatology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryHere, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of the <i>BRAF</i> p.V600E somatic pathogenic variant. In the prospective study, a total of 68 plasma and paired tdDNA samples, and in the retrospective cohort, a total of 100 tdDNA samples were analyzed using dPCR and reverse hybridization StripAssay. The Breslow depth (BD) and Clark level were applied to categorize the study population. Our results demonstrate that dPCR is a highly sensitive and specific method for the detection of <i>BRAF</i> p.V600E somatic variants in cfDNA samples from PCM patients. A strong correlation was detected between BD and cfDNA concentration in all mutant and negative cases, between the tdDNA concentration and the tumor-derived variant allele frequency (VAF) of <i>BRAF</i> p.V600E, between the tdVAF and the cfVAF in all cases, and between the cfDNA and cfVAF in mutant cases. The tdVAF and cfVAF of <i>BRAF</i> p.V600E and cfDNA concentration were the highest in Clark’s V category. The cfDNA concentration was statistically significantly higher in Clark’s III, IV, and V groups compared to cases with a better prognosis. It can also be explained by the fact that cases with a more advanced stage classification release more cfDNA into the peripheral circulation.https://www.mdpi.com/2072-6694/15/21/5141primary cutaneous melanomaBreslow depthClark levelsomatic variant allele frequencycell-free DNA<i>BRAF</i> gene mutation |
| spellingShingle | Szilvia Lilla Csoma Kristóf Madarász Yi Che Chang Chien Gabriella Emri Judit Bedekovics Gábor Méhes Attila Mokánszki Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma Cancers primary cutaneous melanoma Breslow depth Clark level somatic variant allele frequency cell-free DNA <i>BRAF</i> gene mutation |
| title | Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma |
| title_full | Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma |
| title_fullStr | Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma |
| title_full_unstemmed | Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma |
| title_short | Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma |
| title_sort | correlation analyses between histological staging and molecular alterations in tumor derived and cell free dna of early stage primary cutaneous melanoma |
| topic | primary cutaneous melanoma Breslow depth Clark level somatic variant allele frequency cell-free DNA <i>BRAF</i> gene mutation |
| url | https://www.mdpi.com/2072-6694/15/21/5141 |
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