In the 8 patients (4 men) included in analysis, 4 subgroups of CM were observed, including the BRAF V600E mutation in 1 tumor, NRAS Q61R mutation in 3 tumors, NF1 mutations (Q1188X, R440X, or M1215K+ S15fs) in 3 tumors, and triple-wild type (triple-WT) in 1 tumor.
Review of colorectal carcinomas with known KRAS and NRAS genotype revealed that none of 62 wild-type tumors or 47 mutants other than Q61R were SP174 positive.
NGS of the tumor showed an NRAS mutation (c.182A>G:p.Q61R) in 78%, a TP53 mutation (c.856G>A:p.E286K) in 60%, and a TERT gene mutation (1295250C>T) in 28% of the reads.
The primary tumor and all the available metastases exhibited the same molecular oncogenic markers (namely, the RAS mutation p.Q61R and the telomerase promoter mutation C228T).
In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity.
Five of the 7 (71%) responders were BRAF(WT), of which 1 carried c-KIT(L576P) and another N-RAS(Q61R) mutation, while only 2 (29%) of the responding tumors were BRAF(V600E/K).
BRAF V600E mutation was detected in 29% of tumours, 41% of CPTC and 16% of FVPTC; N-RAS Q61R mutation was detected in 6% of tumours, 3% of CPTC and 10% of FVPTC.