Loading
Beyond which KRAS mutation a pancreatic tumour carries, how many copies of the mutant allele it has matters: tumours that lose the normal copy or gain extra mutant copies behave more aggressively and lean towards the basal-like subtype, which is one reason two tumours with the same KRAS mutation can look and behave differently.
Whole-genome sequencing of purified tumour samples in the COMPASS and PanCuRx programmes showed that the balance between the mutant and wild-type KRAS alleles is itself a variable: minor imbalance (more mutant than wild-type copies) and major imbalance (loss of the wild-type allele, often with gain of the mutant one) were associated with the basal-like transcriptional programmes and with worse outcome, while balanced tumours were more often classical (Chan-Seng-Yue 2020). The same study found that classical and basal-like are a continuum, with about 12% of tumours hybrid and intermediate in survival, and that squamous histology is the tissue form of the basal-like signature, often as a subclone. Punctuated evolution explains how imbalance arises: two-thirds of pancreatic cancer genomes show chromothripsis or polyploidy that can change copy number of several drivers at once rather than by stepwise mutation (Notta 2016). In practice routine reports often say only KRAS mutant; allele-level reporting (G12D, G12V, G12R, G12C, Q61) decides which RAS inhibitor applies and carries prognosis, and copy number adds a further layer that no test in routine use reports (the record's open problems). The KRAS allele shares on the record are counts of mutation records over all KRAS mutation records in each cohort.
In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
Showing the target this term concerns: KRAS.
It explains why single-sample classifiers disagree on about one tumour in eight and why KRAS allelic imbalance and GATA6 copy number are being read alongside expression.
The textbook PanIN-to-cancer ladder is only part of the story, and a screening programme cannot assume years of orderly progression in every patient.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Whole-exome & whole-genome sequencing, Pancreatic ductal adenocarcinoma.
Shares KRAS G12D (and other non-G12C KRAS mutations), KRAS mutation subtypes (G12C, G12D, G12V), KRAS, Pancreatic ductal adenocarcinoma.
Shares KRAS G12D (and other non-G12C KRAS mutations), KRAS mutation subtypes (G12C, G12D, G12V), KRAS, Pancreatic ductal adenocarcinoma.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Pancreatic ductal adenocarcinoma.