{"entity":{"id":"paper-almoguera-kras-codon-12-pancreatic-cell-1988","kind":"paper","name":"Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes","aka":[],"tldr":"The 1988 paper that found a mutation in the KRAS gene in 21 of 22 pancreatic cancers, establishing the single most common driver in the disease and the target it took 33 more years to hit.","summary":"Almoguera, Shibata, Forrester, Martin, Arnheim and Perucho used polymerase chain reaction amplification and RNAase A mismatch cleavage to examine c-K-ras in human pancreatic carcinomas, in frozen specimens and single 5 micron sections of formalin-fixed tissue from surgery or autopsy. Twenty-one of 22 carcinomas of the exocrine pancreas carried c-K-ras mutations at codon 12; in seven cases tested the mutation was present in both the primary tumour and its metastases; no mutations were found in normal tissue from the same patients or in five gallbladder carcinomas. The authors concluded that somatic activation of c-K-ras is a critical event in the oncogenesis of most, if not all, cancers of the exocrine pancreas.","asOf":"2026-09-24","links":[{"label":"Cell 1988","url":"https://doi.org/10.1016/0092-8674(88)90571-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2453289/"}],"tags":["pancreatic-evidence"],"related":["kras-roadmap","paper-ostrem-kras-g12c-nature-2013"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":[],"people":["frank-mccormick"],"bottlenecks":["b-undruggable-targets"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":1988,"doi":"10.1016/0092-8674(88)90571-5","pmid":"2453289","authors":"Almoguera C, Shibata D, Forrester K, et al.","paperType":"basic","findings":["21 of 22 exocrine pancreatic carcinomas carried c-K-ras codon 12 mutations.","The mutation was present in both primary and metastasis in all seven pairs tested.","No mutations in matched normal tissue or in five gallbladder carcinomas."],"whatItMeans":"The reason pancreatic cancer is the proving ground for RAS drugs: nearly every tumour depends on the same mutant protein, so a drug that works against it works for nearly every patient.","caveats":["22 tumours from one laboratory; later series put the KRAS mutation rate near 90 percent, with G12D, G12V and G12R the common alleles.","Detection method of its time; the codon 12 mutation subtype was not resolved."],"participants":22},"route":"/key-papers/paper-almoguera-kras-codon-12-pancreatic-cell-1988/","neighbours":{"roadmap":[{"id":"kras-roadmap","kind":"roadmap","name":"KRAS roadmap: undruggable → G12C → pan-RAS","route":"/roadmaps/kras-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"paper":[{"id":"paper-ostrem-kras-g12c-nature-2013","kind":"paper","name":"Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable","route":"/key-papers/paper-ostrem-kras-g12c-nature-2013/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"kras-mutation-subtypes","kind":"term","name":"KRAS mutation subtypes (G12C, G12D, G12V)","route":"/terms/kras-mutation-subtypes/"}],"person":[{"id":"frank-mccormick","kind":"person","name":"Frank McCormick","route":"/people/frank-mccormick/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}]}}