Abstract
Introduction. The concordance of KRAS gene mutation status between the primary and metastatic CRC is 95%. The aim of this study was to find factors associated with the disconcordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in pts with CRC. Patients and methods. We performed DNA melting analysis with TaqMan probes and following Sanger sequencing to detect mutation hot-spots in KRAS exons 2 and 3, NRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20 in 148 tumor tissues from 65 pts (65 primary tumors and 83 metastases). Results. Mutations in KRAS, NRAS, PIK3CA and BRAF genes in primary tumors were detected in 43.1%, 3.1%, 13.8% and 3.1%, respectively. Discordance of mutation status of genes was identified in 29.2% of patients: 16.9% in KRAS, 3% in NRAS, 12.3% in PIK3CA and 3% BRAF status. In all cases of metastases in the brain we found the discordance in KRAS and PIK3CA mutation status (p=0.08). Also, peritoneal metastases had discordance in KRAS status (p=0.02). With the increase of period from removal of the primary tumor and metastases, the incidence rate of changes in the mutational status of the genes also increased. Conclusion. discordance of the mutational status of genes, especially in the long course of the disease, raises the question of repeating biopsies in the progression of the disease
Highlights
The aim of this study was to find factors associated with the discordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in patients with CRC
Mutations in KRAS, NRAS, PIK3CA and BRAF genes were detected in 43.1 %, 3.1 %, 13.8 % and 3.1 %, patients with primary tumors respectively
Discordance of mutation status of genes was identified in 29.2 % of patients: 16.9 % in KRAS, 3 % in NRAS, 12.3 % in PIK3CA and 3 % BRAF status
Summary
Дующей операции по удалению метастазов, мутации в генах KRAS, NRAS, BRAF, PIK3CA обнаруживались у 57,9% (11/19), 5,2% (1/19), 0% и 10,5% (2/19) соответственно. Изменения между первичной опухолью и метастазами по любому из генов в процессе прогрессирования заболевания затрагивали ген KRAS – у 26,3 %, ген NRAS – у 5,2 %, ген PIK3CA – у 21 % больных, суммарно – у 9 из 19 пациентов (47,3 %). Это также поддерживает факт появления в метастазах мутации гена KRAS в метастазе при диком его типе в первичной опухоли. Выявленные нами случаи различного мутационного статуса ряда генов не только между первичной опухолью и метастазами, но и метастазами между собой, отвечают на вопрос о причине встречающейся в клинической практике ситуации с разнонаправленным ответом опухоли на лечение, когда ряд очагов уменьшается, а ряд – растёт. A. et al Concordance of KRAS, NRAS, BRAF, PIK3CA genes mutation status between the primary tumor and metastases in patients with colorectal cancer.
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