Abstract 5134: Biomarker concordance between matched primary and metastatic colorectal tumors

Abstract

Abstract Background: Distant metastasis accounts for ~90% of deaths from colorectal cancer (CRC). The use of biomarkers for targeted therapy in metastatic CRC is well-established, requiring genetic testing of primary or metastatic biopsies. Here we aimed to assess the concordance of actionable alterations in matched primary and metastatic colorectal tumors. Methods: Hybrid capture-based next-generation sequencing (NGS) were performed in a CAP/CLIA-approved laboratory (3DMed). NGS testing for SNV, InDel, CNV, MSI and TMB were performed on 19 primary tumors and 23 matched metastatic biopsies. Results: 42 matched primary and metastatic tumor samples from 19 CRC patients were analyzed. 68.4% of the patients had only liver metastases, 5.3% ovarian metastases, 5.3% peritoneal metastases and 10.5% of the patients had more than one metastatic site. Mutational landscape showed that the primary samples and the metastases shared 80% of top 20 mutations. Biomarker concordance for KRAS was 89.5% (17/19), NRAS was 89.5% (17/19), BRAF was 94.7% (18/19), EGFR was 89.5% (17/19), BRCA2 was 94.7% (18/19) and MS status was 100% (19/19). Inconsistent RAS/BRAF status was found in two liver metastases and one ovarian metastasis. The frequencies of SRC amplification (P = 0.08) and ACVR2A mutation (P = 0.31) seem to be higher in the primary tumors, although these were not statistically significant. Conversely, mutations of NRAS, EGFR and MAP2K4 were detected only in the metastases. One patient harbored EGFR amplification in the ovarian metastasis, while this variant was not present in liver and primary sites. Copy number loss of MAP2K4 was found in the metastatic biopsies of two patients. Tumor mutation burden was comparable between the primary tumors and metastases (3.12 vs 2.17muts/Mb, P=0.29). Conclusions: Our results demonstrates high concordance across multiple biomarkers between the primary and paired metastatic colorectal tumors. Molecular features of ovarian metastasis is more prone to inconsistent with primary sites than liver metastasis, which remains to be further verified in a large population. Citation Format: Yun Yang, Ying Xin, Jianning Song, Chao Jing, Baoyi Zhao, Depei Huang, Wei Deng. Biomarker concordance between matched primary and metastatic colorectal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5134.