KRAS and NRAS mutational analysis in plasma ctDNA from patients with metastatic colorectal cancer by real-time PCR and digital PCR

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Pinheiro, M (Author) Other; Peixoto, A (Author) Other; Rocha, P (Author) Other; Veiga, I (Author) Other; Pinto, C (Author) Other; Santos, C (Author) Other; Pinto, P (Author) Other; Guerra, J (Author) Other; Escudeiro, C (Author) Other; Barbosa, A (Author) Other; Silva, J (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: International Journal of Colorectal Disease

Vol. 37

Pages: 895-905

ISSN: 0179-1958

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00W-B5S

DOI: 10.1007/s00384-022-04126-6

Abstract (EN): Purpose Mutations in the KRAS and NRAS (RAS) genes are negative predictors of response to anti-EGFR therapy in metastatic colorectal cancer (mCRC). The detection of mutations in circulating tumor DNA (ctDNA) has emerged as a less invasive strategy to assess the molecular profile of mCRC patients. We aimed to perform RAS mutational analysis in ctDNA from mCRC patients using BEAMing Digital PCR (OncoBEAM) and Idylla ctDNA qPCR and evaluate the concordance rate with RAS mutational status in tumor tissue and between these two methodologies with different limits of detection. Methods Blood samples were collected from 47 mCRC patients previously tested for RAS mutations in tumor tissue. DNA was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit, and RAS mutation analysis was conducted using OncoBEAM RAS CRC and Idylla ctRAS assays. Results The overall agreement between tumor tissue and ctDNA analyses was 83% and 78.7% using the OncoBEAM and Idylla assays, respectively, with the concordance being 96.2% and 88.5% in naive treatment patients. The overall agreement between OncoBEAM and Idylla ctDNA analyses was 91.7%. Conclusions Analysis of ctDNA is a viable strategy for clinical management of mCRC patients. Although the OncoBEAM assay sensitivity is somewhat higher, the fully automated Idylla platform also has good performance, while being cheaper and much less labor-intensive, for the detection of RAS mutations in plasma, either at diagnosis or after progression when considering anti-EGFR treatment rechallenge.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11