Patterns of Somatic Variants in Colorectal Adenoma and Carcinoma Tissue and Matched Plasma Samples from the Hungarian Oncogenome Program
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Clinical Samples
2.2. DNA Isolation
2.3. Library Preparation and Next-Generation Sequencing
2.4. Bioinformatic Analyses
2.5. Validation of KRAS Mutation Status Using Digital PCR Technology
2.6. In Situ Hybridization
3. Results
3.1. Whole-Exome Sequencing Parameters of Tissue Samples
3.2. COSMIC Mutation Signatures
3.3. Tumor Mutation Burden Evaluation
3.4. Somatic Mutation Landscape of Colorectal Tumors from a Hungarian Cohort
3.5. KRAS Mutation Landscape
3.6. ddPCR and In Situ Hybridization Validation of KRAS G12D
3.7. Whole Exome Sequencing of cfDNA Samples
3.8. CRC-Specific Targeted Sequencing
3.9. Comparison of WES and Targeted Panel Sequencing Results
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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Characteristics | Tissue WES | Plasma WES | Plasma Targeted Panel | |
---|---|---|---|---|
Age | n (Years, (Median)) | n (Years, (Median)) | n (Years, (Median)) | |
N | 18 [21] | 7 [22] | ||
AD | 27 [23] | 17 [23] | ||
CRC | 51 [24] | 33 [69.5] | 11 [25] | |
Sex | n = 92 | n = 57 | n = 11 | |
Male | 48 | 29 | 7 | |
Female | 44 | 28 | 4 | |
Anatomic location of the primary lesion | ||||
AD | n = 27 | n = 17 | ||
Cecum | 1 | 1 | ||
Ascending colon | 1 | |||
Descending colon | 1 | 1 | ||
Sigmoid colon | 6 | 3 | ||
Rectosigmoid | 4 | |||
Rectum | 2 | 1 | ||
Multiple locations | 12 | 11 | ||
CRC | n = 51 | n = 33 | n = 11 | |
Cecum | 10 | 6 | 2 | |
Ascending colon | 5 | 5 | 2 | |
Transverse colon | 3 | 4 | 2 | |
Descending colon | 1 | |||
Sigmoid colon | 11 | 8 | 2 | |
Rectosigmoid | 2 | 1 | ||
Rectum | 16 | 7 | 2 | |
Multiple location | 6 | 3 | 1 | |
Adenoma histology | n = 27 | n = 17 | ||
Tubular | 19 | 13 | ||
Tubulovillous | 5 | 3 | ||
Tubular–tubulovillous | 2 | 1 | ||
CRC AJCC stage | n = 51 | n = 33 | n = 11 | |
I | 5 | 5 | 1 | |
lla | 7 | 8 | 2 | |
llb | 1 | 1 | ||
llla | 9 | 2 | ||
IIIb | 5 | 3 | ||
lllc | 4 | 4 | 1 | |
IV | 17 | 10 | 7 | |
Unkown | 3 |
Hugo_Symbol | SE-CRC | COCA | p-Value | Odds Ratio |
---|---|---|---|---|
ZNF717 | 1 | 73 | 5.70 × 10−5 | 6.11 × 10−2 |
FRG1 | 0 | 55 | 1.06 × 10−4 | 0.00 × 100 |
MUC3A | 0 | 51 | 1.93 × 10−4 | 0 |
MUC6 | 3 | 82 | 3.43 × 10−4 | 1.63 × 10−1 |
KIAA2022 | 8 | 7 | 3.76 × 10−4 | 7.58 × 100 |
DBF4 | 4 | 0 | 4.26 × 10−4 | Inf |
KCNJ12 | 0 | 46 | 5.57 × 10−4 | 0 |
ZSCAN5A | 5 | 2 | 9.68 × 10−4 | 1.57 × 101 |
FNDC3A | 4 | 1 | 1.90 × 10−3 | 2.46 × 101 |
ITGB2 | 4 | 1 | 1.90 × 10−3 | 2.46 × 101 |
OR1M1 | 4 | 1 | 1.90 × 10−3 | 2.46 × 101 |
SMAD3 | 6 | 5 | 2.00 × 10−3 | 7.66 × 100 |
CCDC171 | 5 | 3 | 2.29 × 10−3 | 1.05 × 101 |
LTBP2 | 7 | 8 | 2.56 × 10−3 | 5.66 × 100 |
MUC2 | 2 | 61 | 2.69 × 10−3 | 1.57 × 10−1 |
RP11-764K9.4 | 0 | 39 | 2.82 × 10−3 | 0 |
ALG11 | 3 | 0 | 3.04 × 10−3 | Inf |
CCDC86 | 3 | 0 | 3.04 × 10−3 | Inf |
OC90 | 3 | 0 | 3.04 × 10−3 | Inf |
PRKAR1B | 3 | 0 | 3.04 × 10−3 | Inf |
SLC25A44 | 3 | 0 | 3.04 × 10−3 | Inf |
UBOX5 | 3 | 0 | 3.04 × 10−3 | Inf |
DYNC2H1 | 10 | 18 | 3.30 × 10−3 | 3.73 × 100 |
HLA-DRB1 | 0 | 34 | 4.59 × 10−3 | 0 |
ALDH3A2 | 4 | 2 | 5.06 × 10−3 | 1.23 × 101 |
ALPL | 4 | 2 | 5.06 × 10−3 | 1.23 × 101 |
MFN2 | 4 | 2 | 5.06 × 10−3 | 1.23 × 101 |
SEMG2 | 4 | 2 | 5.06 × 10−3 | 1.23 × 101 |
PTPRU | 6 | 7 | 5.84 × 10−3 | 5.44 × 100 |
RANBP2 | 6 | 7 | 5.84 × 10−3 | 5.44 × 100 |
DPP10 | 7 | 10 | 6.07 × 10−3 | 4.50 × 100 |
FRG2C | 0 | 32 | 7.50 × 10−3 | 0 |
FRG1B | 0 | 31 | 7.66 × 10−3 | 0 |
TNXB | 7 | 11 | 8.81 × 10−3 | 4.08 × 100 |
Hugo_Symbol | SE-CRC | TCGA | p-Value | Odds Ratio |
MUC12 | 4 | 0 | 5.10 × 10−5 | Inf |
ZNF729 | 4 | 0 | 5.10 × 10−5 | Inf |
ENTPD5 | 3 | 0 | 6.21 × 10−4 | Inf |
TRIM49B | 3 | 0 | 6.21 × 10−4 | Inf |
BCL2 | 4 | 2 | 6.70 × 10−4 | 2.24 × 101 |
B4GALNT3 | 5 | 5 | 7.38 × 10−4 | 1.14 × 101 |
NMBR | 5 | 5 | 7.38 × 10−4 | 1.14 × 101 |
FOXD3 | 4 | 3 | 1.46 × 10−3 | 1.50 × 101 |
SLC7A7 | 4 | 3 | 1.46 × 10−3 | 1.50 × 101 |
ZSCAN5A | 5 | 9 | 4.47 × 10−3 | 6.33 × 100 |
ALDH3A2 | 4 | 5 | 4.61 × 10−3 | 8.97 × 100 |
PIK3CA | 4 | 132 | 5.00 × 10−3 | 2.61 × 10−1 |
C1orf43 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
CDT1 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
GPR27 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
KRTAP13-4 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
STMN2 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
ZFHX2 | 3 | 2 | 5.47 × 10−3 | 1.65 × 101 |
SHCBP1L | 5 | 10 | 6.26 × 10−3 | 5.69 × 100 |
AL033381.1 | 2 | 0 | 7.41 × 10−3 | Inf |
ANHX | 2 | 0 | 7.41 × 10−3 | Inf |
ANKRD31 | 2 | 0 | 7.41 × 10−3 | Inf |
C11orf85 | 2 | 0 | 7.41 × 10−3 | Inf |
ERVMER34-1 | 2 | 0 | 7.41 × 10−3 | Inf |
ERVV-1 | 2 | 0 | 7.41 × 10−3 | Inf |
FAM153C | 2 | 0 | 7.41 × 10−3 | Inf |
FAM188B2 | 2 | 0 | 7.41 × 10−3 | Inf |
FBXL8 | 2 | 0 | 7.41 × 10−3 | Inf |
FREM3 | 2 | 0 | 7.41 × 10−3 | Inf |
GCGR | 2 | 0 | 7.41 × 10−3 | Inf |
IZUMO3 | 2 | 0 | 7.41 × 10−3 | Inf |
KRTAP9-1 | 2 | 0 | 7.41 × 10−3 | Inf |
LRRC53 | 2 | 0 | 7.41 × 10−3 | Inf |
MUC22 | 2 | 0 | 7.41 × 10−3 | Inf |
OR56B3P | 2 | 0 | 7.41 × 10−3 | Inf |
PP2D1 | 2 | 0 | 7.41 × 10−3 | Inf |
RP11-10J21.3 | 2 | 0 | 7.41 × 10−3 | Inf |
RP11-766F14.2 | 2 | 0 | 7.41 × 10−3 | Inf |
SAR1B | 2 | 0 | 7.41 × 10−3 | Inf |
STARD9 | 2 | 0 | 7.41 × 10−3 | Inf |
TDRD15 | 2 | 0 | 7.41 × 10−3 | Inf |
TRAV9-1 | 2 | 0 | 7.41 × 10−3 | Inf |
TRIM64C | 2 | 0 | 7.41 × 10−3 | Inf |
YRDC | 2 | 0 | 7.41 × 10−3 | Inf |
ZSCAN5C | 2 | 0 | 7.41 × 10−3 | Inf |
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Kalmár, A.; Galamb, O.; Szabó, G.; Pipek, O.; Medgyes-Horváth, A.; Barták, B.K.; Nagy, Z.B.; Szigeti, K.A.; Zsigrai, S.; Csabai, I.; et al. Patterns of Somatic Variants in Colorectal Adenoma and Carcinoma Tissue and Matched Plasma Samples from the Hungarian Oncogenome Program. Cancers 2023, 15, 907. https://doi.org/10.3390/cancers15030907
Kalmár A, Galamb O, Szabó G, Pipek O, Medgyes-Horváth A, Barták BK, Nagy ZB, Szigeti KA, Zsigrai S, Csabai I, et al. Patterns of Somatic Variants in Colorectal Adenoma and Carcinoma Tissue and Matched Plasma Samples from the Hungarian Oncogenome Program. Cancers. 2023; 15(3):907. https://doi.org/10.3390/cancers15030907
Chicago/Turabian StyleKalmár, Alexandra, Orsolya Galamb, Gitta Szabó, Orsolya Pipek, Anna Medgyes-Horváth, Barbara K. Barták, Zsófia B. Nagy, Krisztina A. Szigeti, Sára Zsigrai, István Csabai, and et al. 2023. "Patterns of Somatic Variants in Colorectal Adenoma and Carcinoma Tissue and Matched Plasma Samples from the Hungarian Oncogenome Program" Cancers 15, no. 3: 907. https://doi.org/10.3390/cancers15030907