Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Case Presentation and Clinical Follow-Up
3.2. NGS-Based Mutation Profiling
3.3. KRAS Validation Studies
3.4. TP53 Gene Sequencing and p53 sTatus
4. Discussion
Author Contributions
Funding
Conflicts of Interest
References
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Time from Primary Surgery (months) | Type of Operation | Histology | Sample ID |
---|---|---|---|
October 2015 | Colon biopsy | Tubular adenoma with high-grade dysplasia | B |
December 2015 | Subtotal colectomy and liver metastasectomy | Colon adenocarcinoma (four independent sites) | T1/1-4 |
Liver metastasis | M1 (M1/1, M1/2) | ||
11 | Hepatic resection | Liver metastasis | M2 |
18 | Hepatic resection | Liver metastasis | M3 |
27 | Hepatic resection | Liver metastasis | M4 (M4/1, M4/2, M4/3) |
36 | Spinal resection and decompression | Adenocarcinoma metastasis | M5 |
Samples | Tumor Cell Content (%) | NGS | NGS VAF (%) | StripAssay | Sanger Sequencing | Sanger VAF (%) |
---|---|---|---|---|---|---|
B | 50 | c.35G > A, p.Gly12Asp | 10.2 | c.35G > A, p.Gly12Asp | NMD b | 0 |
T/1 | 30 | c.35G > A; p.Gly12Asp | 40.6 | c.35G > A; p.Gly12Asp | c.35G > A; p.Gly12Asp | 10 |
T/2 | 50 | NMD a | 0 | NMD a | NMD a | 0 |
T/3 | 30 | c.34G > T; p.Gly12Cys | 16.2 | c.34G > T; p.Gly12Cys | NMD | 0 |
T/4 | 30 | c.35G > T; p.Gly12Val | 15.1 | c.35G > T; p.Gly12Val | c.35G > T; p.Gly12Val | 26.86 |
M1/1 | 20 | NMD a | 0 | c.34G > T; p.Gly12Cys b | NMD a | 0 |
M1/2 | 30 | c.34G > T; p.Gly12Cys | 19.1 | c.34G > T; p.Gly12Cys | c.34G > T; p.Gly12Cys | 45.89 |
M2 | 20 | c.34G > T; p.Gly12Cys | 6.4 | c.34G > T; p.Gly12Cys | NMD | 0 |
M3 | 30 | NMD a | 0 | NMD a | NMD a | 0 |
M4/1 | 30 | c.34G > T; p.Gly12Cys | <2 | c.34G > T; p.Gly12Cys | NMD | 0 |
M4/2 | c.34G > T; p.Gly12Cys | <2 | c.34G > T; p.Gly12Cys | c.34G > T; p.Gly12Cys | 9.77 | |
30 | c.35G > A; p.Gly12Asp | <2 | ||||
c.35G > T; p.Gly12Val | <2 | |||||
M4/3 | 30 | c.34G > T; p.Gly12Cys | 5.3 | c.34G > T; p.Gly12Cys | NMD | 0 |
M5 | 50 | c.34G > T; p.Gly12Cys | 32.1 | c.34G > T; p.Gly12Cys | c.34G > T; p.Gly12Cys | 52 |
Sample | NGS | NGS VAF (%) | Mitosis Index | p53 IHC (%) | p53 H-Score | p53 Interpretation | Clinical Significance (COSMIC) | Clinical Significance (ClinVar) |
---|---|---|---|---|---|---|---|---|
Biopsy | c.417G > A; p.Lys139Asn | 2.9 | 24 | 2 | 5 | WT | P | ND |
c.472C > T; p.Arg158Cys | 3.8 | P | C | |||||
c.1009C > T; p.Arg337Cys | 3.1 | P | P | |||||
c.464C > T; p.Thr155Ile | 7.6 | N | ND | |||||
T/1 | c.455C > T, p.Pro152Leu | 3.3 | 62 | 5 | 23 | WT | P | ND |
c.845G > A, p.Arg282Gln | 3.9 | P | C | |||||
T/2 | c.557C > G; p.His193Asp | 35.6 | 71 | 60 | 155 | M | ND | LP |
c.586C > T; p. Arg196* | 5.6 | P | P | |||||
T/3 | c.820G > T; p.Val274Phe | 33.3 | 50 | 90 | 230 | M | N | LP |
T/4 | c.743G > A; p.Arg248Gln | 3.1 | 62 | 15 | 25 | WT | P | P |
M1/1 | c.726C > A; p.Cys242* | 10.8 | 57 | 70 | 150 | M | P | ND |
c.769G > A; p.Gly266Arg | 7.4 | ND | C | |||||
c.328C > T; p.Arg110Cys | 8.3 | ND | US | |||||
c.747G > T; p.Arg249Ser | 4.0 | ND | C | |||||
c.820G > T, p.Val274Phe | 23.1 | N | LP | |||||
M1/2 | c.827C > T; p.Ala276Val | 15.7 | 64 | 100 | 300 | M | ND | ND |
c.917G > A; p.Arg306Gln | 28.1 | P | C | |||||
c.820G > T; p.Val274Phe | 6.1 | N | LP | |||||
M2 | c.820G > T; p.Val274Phe | 7.1 | 31 | 90 | 225 | M | N | LP |
M3 | c.820G > T; p.Val274Phe | 3.14 | 30 | 80 | 195 | M | N | LP |
M4/1 | c.820G > T; p.Val274Phe | 37.9 | 62 | 80 | 195 | M | N | LP |
M4/2 | c.820G > T; p.Val274Phe | 72.8 | 91 | 100 | 300 | Mutant | N | LP |
M4/3 | c.820G > T; p.Val274Phe | 25.2 | 46 | 100 | 300 | Mutant | N | LP |
M5 | c.820G > T; p.Val274Phe | 45.6 | 24 | 100 | 300 | Mutant | N | LP |
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Bádon, E.S.; Mokánszki, A.; Mónus, A.; András, C.; Damjanovich, L.; Méhes, G. Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling. Diagnostics 2020, 10, 407. https://doi.org/10.3390/diagnostics10060407
Bádon ES, Mokánszki A, Mónus A, András C, Damjanovich L, Méhes G. Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling. Diagnostics. 2020; 10(6):407. https://doi.org/10.3390/diagnostics10060407
Chicago/Turabian StyleBádon, Emese Sarolta, Attila Mokánszki, Anikó Mónus, Csilla András, László Damjanovich, and Gábor Méhes. 2020. "Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling" Diagnostics 10, no. 6: 407. https://doi.org/10.3390/diagnostics10060407