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The normal, unmutated version of a gene. Saying a tumour is 'RAS wild-type' means its RAS gene is not mutated, which for colorectal cancer means EGFR antibodies can work.
Borrowed from genetics, wild-type is the reference sequence against which mutations are defined. It matters when a mutation predicts resistance rather than sensitivity: only RAS/BRAF wild-type colorectal cancers respond to cetuximab or panitumumab; TP53 wild-type tumours can respond to MDM2 inhibitors; unmutated IGHV in CLL predicts shorter remissions with chemoimmunotherapy. Because 'wild-type' depends on what was tested, a tumour can be wild-type on a small panel and mutated on a larger one.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
This is the paper Europe PMC returns for registry id NCT02394795 with the most citations, so it is the natural first reading for anyone following the PARADIGM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
Together with the German MASTER report, this paper is why guidelines recommend comprehensive profiling with fusion detection in KRAS wild-type pancreatic cancer.
It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.
KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.
It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.
It is the reference for what a colorectal molecular report must contain, and the document that turned extended RAS from a trial finding into a requirement.
Shares Molecular biomarkers for the evaluation of colorectal cancer: guideline from ASCP, CAP, AMP and ASCO, NRAS, RAS wild-type (extended KRAS and NRAS testing), EGFR.
Shares eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer, Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma, Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma.
Shares Molecular biomarkers for the evaluation of colorectal cancer: guideline from ASCP, CAP, AMP and ASCO, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, RAS wild-type (extended KRAS and NRAS testing), Comprehensive genomic profiling.
Shares K-ras mutations and benefit from cetuximab in advanced colorectal cancer, KRAS G12D (and other non-G12C KRAS mutations), Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), RAS wild-type (extended KRAS and NRAS testing).
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials, RAS wild-type (extended KRAS and NRAS testing).
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME).
Shares eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer, Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma, Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer, Integrated genomic characterization of pancreatic ductal adenocarcinoma.
Shares NRAS, RAS wild-type (extended KRAS and NRAS testing), EGFR, KRAS.