Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors
A partir de 265 paires d'échantillons de tumeurs primitives et de métastases prélevés sur des patients atteints d'une tumeur solide, cette étude identifie notamment des mutations des gènes PIK3CA, SMAD4 et TP53 présentes spécifiquement dans les métastases
Purpose: We used a clinical next-generation sequencing hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design: A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type, percentage tumor, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results: 227 (85.7%) of 265 tumor-metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) cases did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n=20, 7.5%) than primary tumors (n=12, 4.5%). TP53 was the most commonly additionally mutated gene, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions: Clinical next-generation sequencing hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4 and TP53 are most often involved in clonal divergence, providing potential targets that may help with metastatic control.