Comprehensive assessment of actionable genomic alterations in primary colorectal carcinoma using targeted next-generation sequencing
Menée à partir de l'analyse de 575 échantillons tumoraux issus de patients atteints d'un cancer colorectal, cette étude examine la présence d'une instabilité des microsatellites, évalue la charge mutationnelle des tumeurs et identifie des altérations génomiques pouvant compromettre l'efficacité d'inhibiteurs de point de contrôle immunitaire ou de traitements anti-EGFR
Background : The clinical utility of comprehensive genomic profiling (CGP) for guiding treatment has gradually become the standard-of-care procedure for colorectal carcinoma (CRC). Here, we comprehensively assess emerging targeted therapy biomarkers using CGP in primary CRC.
Methods : A total of 575 primary CRCs were sequenced by ACTOnco® assay for genomic alterations, tumour mutational burden (TMB), and microsatellite instability (MSI).
Results : Eighteen percent of patients were detected as MSI-High (MSI-H), and the remaining cases were classified as microsatellite stable (MSS). Driver mutation prevalence in MSS CRCs were APC (74%), TP53 (67%), KRAS (47%), PIK3CA (21%) and BRAF (13%). The median TMBs for MSI-H and MSS patients were 37.8 mutations per mega base (mut/Mb) and 3.9 mut/Mb, respectively. Forty-seven percent of MSI-H CRC harboured at least one loss-of-function mutations in genes that may hamper immune checkpoint blockade. Among MSS RAS/RAF wild-type CRCs, 59% had at least one actionable mutation that may compromise the efficacy of anti-EGFR therapy. For late-stage CRC, 51% of patients are eligible for standard care actionability and the remaining 49% could be enrolled in clinical trials with investigational drugs.
Conclusions : This study highlights the essential role of CGP for identifying rational targeted therapy options in CRC.
British Journal of Cancer , article en libre accès, 2022