Abstract 2084
Background
KRAS and NRAS mutations render resistance to EGFR therapeutic antibodies. Some data indicate that erroneous administration of cetuximab or panitumumab to patients with RAS-mutated colorectal cancer (CRC) may even accelerate tumour growth.
Methods
1501 CRC patients were included in the analysis. High-resolution melting (HRM) was performed for the initial screening of KRAS and NRAS mutations in exons 2, 3 and 4. Common RAS mutations were detected by allele-specific PCR, then the remaining samples were analysed by pyrosequencing.
Results
RAS mutations were identified in 756 (50.4%) CRCs. KRAS and NRAS alterations were generally mutually exclusive, with the exception of 2 CRCs carrying lesions in both oncogenes. Distribution or RAS mutations did not show correlation with age or gender. Significant number of the revealed mutations are not included in the spectrum of substitutions covered by commercial kits. For 681 identified KRAS mutations, the following coverage is expected according to manufacturer’s brochures: Therascreen (Qiagen): 592 (86.9%); cobas® (Roche, US version): 615 (90.3%); AmoyDx: 665 (97.7%); KRAS StripAssay® (ViennaLab): 600 (88.1%); KRAS XL StripAssay® (ViennaLab): 671 (98.5%). For 77 detected NRAS mutations, these estimates would be 73 (94.8%) for AmoyDx and 75 (97.4%) for NRAS XL StripAssay® (ViennaLab).
Conclusions
Clinically significant share of KRAS and NRAS mutations is likely to be missed by conventional mutation-specific diagnostic kits. This limitation has to be considered while defining diagnostic standards for CRC therapy.
Clinical trial identification
Legal entity responsible for the study
Evgeny Imyanitov.
Funding
Russian Society of Clinical Oncology.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4162 - ODM-207 - a novel BET bromodomain inhibitor with antitumor activity in nonclinical models of ER+ breast cancer
Presenter: Anu Moilanen
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3747 - HER2-positive breast cancer resistance to trastuzumab is associated with metabolic switch.
Presenter: Roman Dubianski
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4688 - Combination treatment with the PARP inhibitor niraparib and chemotherapeutics in a preclinical model of KRAS/BRAF mutated colorectal cancer cell lines across the four Consensus Molecular Subtypes.
Presenter: Pietro Paolo Vitiello
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
498 - Exosomal microRNA-32-5p induces multidrug resistance in hepatocellular carcinoma via the PI3K/Akt pathway.
Presenter: Xiao Fu
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3731 - Effect of the polymorphism rs2470893 of the CYP1A1 gene on ovarian and endometrial cancer in Mediterranean women
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1215 - Cisplatin in NIPEC or HIPEC?
Presenter: Ivan Alvovsky
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2738 - Matrix metalloproteinase-mediated regulation of programmed-death ligand in the human head and neck squamous cell carcinoma microenvironment
Presenter: MARIKO HIRAI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2190 - Trametinib synergizes with dexamethasone in KRAS-mutant myeloma cell lines through modulation of NDRG1 and induction of apoptosis
Presenter: Priya Sriskandarajah
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4482 - Functional inhibition of TGF-_ in colorectal cancer cells and its interaction with AXL receptor
Presenter: Davide Ciardiello
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
624 - Isoform-specific AKT Inhibition Differentially Affects Cell Functions in Pancreatic Adenocarcinoma
Presenter: Hugo Arasanz
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract