# Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes

Source: https://onco.cc/key-papers/paper-almoguera-kras-codon-12-pancreatic-cell-1988/  
OnCo record `paper-almoguera-kras-codon-12-pancreatic-cell-1988` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: pancreatic-evidence
- Journal: Cell
- Year: 1988
- DOI: 10.1016/0092-8674(88)90571-5
- Authors: Almoguera C, Shibata D, Forrester K, et al.
- 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.
- What it means: 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.

## Sources

- Cell 1988: https://doi.org/10.1016/0092-8674(88)90571-5
- PubMed: https://pubmed.ncbi.nlm.nih.gov/2453289/

## Connected records

- roadmaps: [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- key papers: [Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable](https://onco.cc/key-papers/paper-ostrem-kras-g12c-nature-2013/)
- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/)
- people: [Frank McCormick](https://onco.cc/people/frank-mccormick/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- journals: [Cell](https://onco.cc/journals/cell/)

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