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Updated: Jan 9, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Genomic divergence between matched primary and metastatic tumors across cancer types: a pan-cancer analysis of 5,692
1Department of Medical Oncology, Bower Hospital, Diyarbakır, Turkey.
Background:
Metastasis is the leading cause of cancer-related death and involves biological processes such as genomic instability and immune evasion. Although metastatic tumors generally retain major alterations present in primary tumors, the extent of additional genomic divergence across cancer types remains insufficiently characterized.
Research Design And Methods:
A pan-cancer analysis was performed using targeted sequencing data from 2846 patients with matched primary and metastatic tumors (5692 samples) from the AACR Project GENIE-v18.0 cohort. Comparisons between primary and metastatic samples included mutation count, fraction of genome altered (FGA), gene-level mutation frequencies, copy number alterations (CNA), and structural variants (SV).
Results:
Metastatic tumors showed modest but statistically significant increases in mutation count (median 6 vs. 5) and FGA (0.186 vs. 0.140), with the largest differences observed in lung, breast, colorectal, pancreatic, and prostate cancers. Eleven genes, including KDM5A, CDKN2A, MYC, ESR1, and AR, were more frequently altered in metastases. Differences in CNA and SV patterns were also observed, particularly in genes involved in cell cycle control and DNA repair.
Conclusions:
Compared with primary tumors, metastatic tumors demonstrated small but consistent genomic differences. These findings varied across cancer types and may reflect changes associated with the evolutionary transition from primary to metastatic disease.
Insights
Metastatic tumors exhibit small but significant genomic differences compared to primary tumors, with notable variations across cancer types. These genomic changes may reflect tumor evolution during metastasis.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Metastasis is the primary cause of cancer mortality.
- Genomic instability and immune evasion are key metastatic processes.
- Genomic divergence between primary and metastatic tumors requires further characterization.
Purpose of the Study:
- To perform a pan-cancer analysis of genomic differences between primary and metastatic tumors.
- To compare mutation counts, genome-wide alterations, and structural variants in matched tumor samples.
Main Methods:
- Utilized targeted sequencing data from 2846 patients with matched primary and metastatic tumors (AACR Project GENIE-v18.0).
- Compared mutation count, fraction of genome altered (FGA), gene mutations, copy number alterations (CNA), and structural variants (SV).
Main Results:
- Metastatic tumors showed modest increases in mutation count (median 6 vs. 5) and FGA (0.186 vs. 0.140).
- Lung, breast, colorectal, pancreatic, and prostate cancers exhibited the largest genomic differences.
- Eleven genes, including KDM5A, CDKN2A, MYC, ESR1, and AR, were more frequently altered in metastases. CNA and SV patterns also differed, particularly in cell cycle and DNA repair genes.
Conclusions:
- Metastatic tumors display small but consistent genomic differences compared to primary tumors.
- These genomic variations differ across cancer types.
- Findings suggest evolutionary changes during the transition from primary to metastatic disease.
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