Genomic Landscape of Actionable Mutations in Primary and Metastatic Tissues of Colon Adenocarcinoma

Abstract

Aim To assess the actionable genomic landscape of colon adenocarcinoma in the primary and metastatic tumor tissues. Methods The data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) were used in this study. Colon adenocarcinoma patients with primary and metastatic tissue samples (distant organ and lymph node) were selected. Patients with samples from a local recurrence, not otherwise specified tumor samples, and data not collected for sampling localization were excluded. Results A total of 3286 and 1727 patients were included in the primary and metastatic tissue sample groups, respectively. There was no difference between the groups in Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation rates. The rates of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and mismatch repair (MMR) gene mutations were higher in the primary tumor tissues than in the metastatic tumor tissues. There was also no difference between the groups in other actionable gene alterations (e.g. ERBB2 amplification and neurotrophic receptor tyrosine kinase (NTRK) 1 and NTRK3 fusions). In contrast to all cohorts, in Asian and black patients, there was no difference in actionable genomic landscape between the primary and metastatic tumor tissues. Conclusion This study had the largest number of colon cancer patients that evaluated the actionable genomic alterations in primary and metastatic tumor tissues. BRAF and MMR gene alterations were more frequent in the primary tumor tissues than the metastatic tumor tissues.

Keywords: braf mutation; colorectal neoplasms; genomics; k-ras mutations; neoplasm metastasis.

Figure 1. Genomic alterations in each gender

Blue bars represent primary tumor tissue and red bars represent metastatic tumor tissue. Numbers inside the bars indicate patients with genomic alteration and numbers outside the bars indicate all patients with genomic analysis. * Difference between the groups was statistically significant. KRAS: Kirsten rat sarcoma viral oncogene homolog; NRAS: neuroblastoma RAS viral oncogene homolog; BRAF: v-Raf murine sarcoma viral oncogene homolog B.

Figure 2. Genomic alterations in each race

Blue bars represent primary tumor tissue and red bars represent metastatic tumor tissue. Numbers inside the bars indicate patients with genomic alteration and numbers outside the bars indicate all patients with genomic analysis. * Difference between the groups was statistically significant. KRAS: Kirsten rat sarcoma viral oncogene homolog; NRAS: neuroblastoma RAS viral oncogene homolog; BRAF: v-Raf murine sarcoma viral oncogene homolog B.