Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation Sequencing
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients Samples
2.2. Tumor Volume Evaluation
2.3. Histology and Immunohistochemistry
2.4. DNA Isolation
2.5. Next-Generation Sequencing
2.6. Statistical Analysis
3. Results
3.1. Patients Clinicopathological Characteristics
3.2. Histological Features including Immunohistochemistry
3.3. Correlation Analysis between Estimated Tumor Volume and cfDNA Yield
3.4. NGS-Based Mutation Profiling of Genomic and Cell-Free DNA
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cases | Gender | Age (Years) | ETV (mm3) | Metastasis | BTC Subtype | Chemotherapy |
---|---|---|---|---|---|---|
1 | F | 80 | 83,349 | no | IHCC | cisplatin plus gemcitabine, capecitabine, irinotecan |
2 | F | 75 | 88,200 | liver | IHCC | gemcitabine, bevacizumab |
3 | M | 76 | 56,784 | liver | IHCC | capecitabine, cisplatin plus gemcitabin |
4 | M | 59 | 37,044 | no | IHCC | cisplatin plus gemcitabine |
5 | M | 68 | 1,680,000 | no | IHCC | cisplatin plus gemcibatine, irinotecan, capecitabine |
6 | M | 68 | 37,462 | no | IHCC | cisplatin plus gemcitabine, capecitabine |
7 | M | 60 | 259,200 | peritoneum | IHCC | cisplatin plus gemcitabine, trametinib, everolimus |
8 | M | 68 | 62,500 | no | IHCC | cisplatin plus gemcitabine |
9 | F | 63 | 1,230,187 | no | IHCC | cisplatin plus gemcitabine |
10 | M | 53 | 263,250 | no | IHCC | cisplatin plus gemcitabine, irinotecan |
11 | M | 70 | 12,800 | no | IHCC | cisplatin plus gemcitabine, irinotecan, capeticabine |
12 | F | 61 | 283,500 | no | IHCC | cisplatin plus gemcitabine, capecitabine |
13 | M | 75 | 9126 | liver | IHCC | capecitabine, gemcitabine |
14 | F | 49 | 140,625 | ovary | IHCC | cisplatin plus gemcitabine |
15 | F | 66 | 670,372 | no | IHCC | gemcitabine |
16 | F | 64 | 36,162 | no | EHCC | cisplatin plus gemcitabine, capecitabine |
17 | M | 43 | 952,544 | no | EHCC | cisplatin plus gemcitabine, irinotecan |
18 | M | 51 | 6664 | no | EHCC | cisplatin plus gemcitabine, nivolumab |
19 | F | 70 | 98,606 | no | EHCC | cisplatin plus gemcitabine |
20 | F | 71 | 32,000 | no | EHCC | cisplatin plus gemcitabine |
21 | F | 58 | 6750 | no | GBC | cisplatin plus gemcitabine, irinotecan |
22 | M | 70 | 126,000 | no | GBC | cisplatin plus gemcitabine |
23 | M | 68 | 3179 | no | GBC | cisplatin plus gemcitabine |
24 | F | 71 | 137,312 | no | GBC | cisplatin plus gemcitabine |
25 | F | 60 | 98,000 | no | GBC | capecitabine, cisplatin plus gemcitabine |
Cases | Grading | CK7 | CK8/18 | CK19 | CK20 | CA19.9 | HSA | Arginase | Glypican | PD-L1 |
---|---|---|---|---|---|---|---|---|---|---|
1 | G2 | + | + | + | − | + | − | − | − | − |
2 | G2 | + | + | + | + | + | − | − | − | − |
3 | G3 | + | + | + | − | + | − | − | − | − |
4 | G2 | + | + | + | − | + | − | − | − | − |
5 | G2 | + | + | + | − | + | − | − | − | − |
6 | G2 | + | − | + | − | + | − | − | − | − |
7 | G2 | + | + | + | − | + | − | − | − | − |
8 | G2 | + | + | + | − | + | − | − | + * | − |
9 | G2 | + | + | + | + | + | − | − | − | − |
10 | G2 | + | + | + | − | + | − | − | − | − |
11 | G2 | + | + | + | − | + | − | + | − | − |
12 | G3 | + | + | + | + | + | − | − | − | − |
13 | G2 | + | + | + | − | − | − | − | − | − |
14 | G3 | + | + | + | − | + | − | − | + * | − |
15 | G2 | + | − | + | − | + | − | − | − | − |
16 | G1 | + | + | + | − | + | − | − | − | − |
17 | G3 | + | + | + | − | + | − | − | − | − |
18 | G2 | − | + | + | − | + | − | − | − | − |
19 | G2 | + | + | + | − | − | − | − | − | − |
20 | G2 | + | + | + | − | + | − | − | − | − |
21 | G2 | + | + | + | − | + | − | − | − | − |
22 | G2 | + | + | + | + | + | − | − | − | − |
23 | G3 | + | + | + | − | + | − | + | − | − |
24 | G3 | + | + | + | − | + | − | + | − | − |
25 | G2 | + | + | + | − | + | − | − | − | − |
Cases | Gene | Nucleotide Change | Amino Acid Change | VAF (%) Tissue | VAF (%) LB | Clinical Significance |
---|---|---|---|---|---|---|
2 | KRAS | c.407G>A | p.Ser136Asn | 50 | 21.3 | pathogenic |
IDH1 | c.395G>T | p.Arg132Leu | 25 | 19.6 | pathogenic | |
PTEN | c.925G>A | p.Ala309Thr | 20 | 15.2 | benign | |
FBXW7 | c.239C>T | p.Thr80Ile | 6 | 0 | likely pathogenic | |
IDH2 | c.332G>A | p.Gly111Asp | 4.6 | 0 | likely benign | |
CDH1 | c.596C>T | p.Thr199Ile | 4.3 | 0 | likely benign | |
3 | PIK3CA | c.1634A>C | p.Glu545Ala | 3 | 3 | pathogenic |
6 | FOXL2 | c.536C>G | p.Ala179Gly | 57.6 | 15.2 | benign |
APC | c.7504G>A | p.Gly2502Ser | 49.5 | 6.7 | likely pathogenic | |
PIK3CA | c.1634A>C | p.Glu545Ala | 3.8 | 0 | pathogenic | |
7 | JAK3 | c.2164G>A | p.Val722Ile | 45.5 | 6.9 | benign |
TP53 | c.518T>C | p.Val173Ala | 13.2 | 4.9 | pathogenic | |
KRAS | c.35G>T | p.Gly12Val | 12.8 | 3.6 | pathogenic | |
8 | TP53 | c.460G>A | p.Gly154Ser | 4 | 2.1 | pathogenic |
9 | FGFR2 | c.827T>G | p.Phe276Cys | 37 | 6.3 | pathogenic |
10 | IDH2 | c.515G>T | p.Arg172Met | 24.3 | 21.5 | pathogenic |
11 | IDH2 | c.359G>A | p.Arg120Lys | 27.6 | 8.4 | pathogenic |
12 | KDR | c.1444T>C | p.Cys482Arg | Low tumor cell ratio | 47.2 | pathogenic |
STK11 | c.1189G>A | p.Ala397Thr | 46.3 | benign | ||
13 | TP53 | c.536A>G | p.His179Arg | 62.6 | 5.6 | pathogenic |
IDH2 | c.359G>A | p.Arg120Lys | 30.2 | 4.2 | pathogenic | |
14 | MET | c.2975C>T | p.Thr992Ile | 0 | 45.8 | pathogenic |
15 | CSF1R | c.2916C>G | p.Cys972Trp | 0 | 7.9 | benign |
RET | c.1946C>T | p.Ser649Leu | 0 | 7.8 | likely pathogenic | |
FOXL2 | c.536C>G | p.Ala179Gly | 61.6 | 4.5 | benign | |
16 | TP53 | c.796G>T | p.Gly266Ter | 29.2 | 5.2 | pathogenic |
18 | MET | c.1124A>G | p.Asn375Ser | 59.7 | 48.21 | pathogenic |
HRAS | c.182A>G | p.Gln61Arg | 33.3 | 0 | pathogenic | |
PIK3CA | c.40C>A | p.His14Asn | 7.2 | 0 | likely benign | |
PIK3CA | c.1634A>C | p.Glu545Ala | 4.6 | 0 | pathogenic | |
20 | FOXL2 | c.536C>G | p.Ala179Gly | Low tumor cell ratio | 67.5 | benign |
PIK3CA | c.1571G>A | p.Arg524Lys | 7.7 | pathogenic | ||
21 | NRAS | c.104C>T | p.Thr35Ile | 8.3 | 2.6 | benign |
22 | CDKN2A | c.442G>A | p.Ala148Thr | 57.8 | 52 | benign |
EGFR | c.2543C>T | p.Pro848Leu | 41 | 39 | likely benign | |
23 | CDKN2A | c.442G>A | p.Ala148Thr | 49 | 52.8 | benign |
CDH1 | c.2474C>T | p.Pro825Leu | 46 | 50.7 | pathogenic | |
HNF1A | c.862delG | p.Pro291GlnfsTer51 | 5.2 | 5.14 | likely pathogenic | |
TP53 | c.325T>G | p.Phe109Val | 4.9 | 0 | pathogenic | |
PTEN | c.802G>T | p.Asp268Tyr | 4.6 | 0 | pathogenic | |
24 | STK11 | c.842del | p.Pro281ArgfsTer6 | 6.3 | 0 | pathogenic |
25 | MLH1 | c.1321G>A | p.Ala441Thr | 46.2 | 49.1 | pathogenic |
TP53 | c.707_711del | p.Tyr236LeufsTer2 | 12.1 | 3.4 | likely pathogenic | |
PIK3CA | c.1571G>A | p.Arg524Lys | 11.3 | 5.3 | pathogenic | |
CTNNB1 | c.133T>C | p.Ser45Pro | 11.2 | 2.4 | pathogenic | |
KRAS | c.34G>T | p.Gly12Cys | 6.6 | 0 | pathogenic | |
FOXL2 | c.743T>C | p.Leu248Pro | 0 | 3.1 | likely pathogenic |
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Csoma, S.L.; Bedekovics, J.; Veres, G.; Árokszállási, A.; András, C.; Méhes, G.; Mokánszki, A. Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation Sequencing. Cancers 2022, 14, 233. https://doi.org/10.3390/cancers14010233
Csoma SL, Bedekovics J, Veres G, Árokszállási A, András C, Méhes G, Mokánszki A. Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation Sequencing. Cancers. 2022; 14(1):233. https://doi.org/10.3390/cancers14010233
Chicago/Turabian StyleCsoma, Szilvia Lilla, Judit Bedekovics, Gergő Veres, Anita Árokszállási, Csilla András, Gábor Méhes, and Attila Mokánszki. 2022. "Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation Sequencing" Cancers 14, no. 1: 233. https://doi.org/10.3390/cancers14010233