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Purpose

The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication.

Materials and Methods

Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites.

Results

A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases.

Conclusion

Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

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참고문헌 (30건) : 자료제공( 네이버학술정보 )

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번호 참고문헌 국회도서관 소장유무
1 Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 네이버 미소장
2 Riihimaki M, Thomsen H, Sundquist K, Hemminki K. Colorectal cancer patients: what do they die of? Frontline Gastroenterol. 2012;3:143-9. 미소장
3 Oligometastases. 네이버 미소장
4 Oligometastases revisited 네이버 미소장
5 Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases 네이버 미소장
6 de Baere T, Auperin A, Deschamps F, Chevallier P, Gaubert Y, Boige V, et al. Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases. Ann Oncol. 2015;26:987-91. 미소장
7 The concept of oligometastases in colorectal cancer: from the clinical evidences to new therapeutic strategies. 네이버 미소장
8 Predictors of Recurrent Pulmonary Metastases and Survival After Pulmonary Metastasectomy for Colorectal Cancer 네이버 미소장
9 Early recurrence in patients undergoing curative resection of colorectal liver oligometastases: identification of its clinical characteristics, risk factors, and prognosis. 네이버 미소장
10 Mutational profile of colorectal cancer lung metastases and paired primary tumors by targeted next generation sequencing: implications on clinical outcome after surgery. 네이버 미소장
11 Prognostic and predictive markers in liver limited stage IV colorectal cancer 네이버 미소장
12 Pitroda SP, Khodarev NN, Huang L, Uppal A, Wightman SC, Ganai S, et al. Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nat Commun. 2018;9:1793. 미소장
13 Tumour heterogeneity. 네이버 미소장
14 Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. 네이버 미소장
15 Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma. 네이버 미소장
16 Evolving concepts of tumor heterogeneity. 네이버 미소장
17 Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification. 네이버 미소장
18 Mutations of key driver genes in colorectal cancer progression and metastasis 네이버 미소장
19 Schlussel AT, Donlon SS, Eggerding FA, Gagliano RA. Identification of an APC variant in a patient with clinical attenuated familial adenomatous polyposis. Case Rep Med. 2014;2014:432324. 미소장
20 Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing 네이버 미소장
21 Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. 네이버 미소장
22 New paradigms in clonal evolution: punctuated equilibrium in cancer 네이버 미소장
23 A Big Bang model of human colorectal tumor growth. 네이버 미소장
24 Mutations in the RAS‐MAPK, PI(3)K (phosphatidylinositol‐3‐OH kinase) signaling network correlate with poor survival in a population‐based series of colon cancers 네이버 미소장
25 Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. 네이버 미소장
26 Cai J, Xia L, Li J, Ni S, Song H, Wu X. Tumor-associated macrophages derived TGF-betaInduced epithelial to mesenchymal transition in colorectal cancer cells through Smad2,3-4/Snail signaling pathway. Cancer Res Treat. 2019;51:252-66. 미소장
27 Tumor Heterogeneity Predicts Metastatic Potential in Colorectal Cancer. 네이버 미소장
28 Coaltered Ras/B-raf and TP53 Is Associated with Extremes of Survivorship and Distinct Patterns of Metastasis in Patients with Metastatic Colorectal Cancer. 네이버 미소장
29 The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. 네이버 미소장
30 Supek F, Minana B, Valcarcel J, Gabaldon T, Lehner B. Synonymous mutations frequently act as driver mutations in human cancers. Cell. 2014;156:1324-35. 미소장

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