# KIT exon 11-mutant GIST

Source: https://onco.cc/cancers/gist-kit-exon-11/  
OnCo record `gist-kit-exon-11` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Most GISTs are driven by a mutation in exon 11 of the KIT gene, which keeps the KIT growth receptor switched on. Imatinib blocks it: given for three years after surgery in higher-risk tumours it prevents relapse and extends life, and in metastatic disease it controls the tumour for years before resistance develops.

## Summary

Gastrointestinal stromal tumours arise from the interstitial cells of Cajal in the gut wall, and in 1998 Hirota showed that most carry activating mutations of KIT. Exon 11 mutations, which affect the juxtamembrane domain that normally holds the receptor inactive, account for around two thirds of all GISTs, occur at every site, and are the most sensitive to imatinib at 400 mg daily. Deletions involving codons 557 and 558 carry a worse prognosis than substitutions. Mutation testing is required before treatment because exon 9, PDGFRA D842V and wild-type tumours behave differently, and risk of relapse after surgery is estimated from size, mitotic count and site using the Miettinen or modified NIH criteria.

Surgery removes localised tumours with clear margins and without lymph node dissection, since GIST rarely spreads to nodes. Adjuvant imatinib for one year improved recurrence-free survival in ACOSOG Z9001 (2009), and the Scandinavian SSG XVIII trial (JAMA 2012) showed that three years beat one in high-risk tumours, with five-year overall survival of 92 percent against 82 percent; three years is standard for high-risk disease, and trials of five years are ongoing. Neoadjuvant imatinib shrinks large or awkwardly placed tumours, at the rectum or gastro-oesophageal junction, to allow organ-sparing surgery.

In metastatic disease imatinib controls the tumour for a median of around two years before secondary mutations, in the ATP-binding pocket (exons 13 and 14) or activation loop (exons 17 and 18), cause resistance; the drug is continued indefinitely because stopping it leads to rapid progression. Response is judged on CT with Choi criteria, since tumours may become cystic without shrinking. On progression, dose escalation to 800 mg, then sunitinib, regorafenib and ripretinib follow, and circulating tumour DNA is increasingly used to identify the secondary mutation and choose between them.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Imatinib-sensitive GIST; KIT-mutant gastrointestinal stromal tumour; Classic GIST
- Tags: subtype-page
- Group: gastrointestinal
- Burden: About two thirds of gastrointestinal stromal tumours carry a mutation in exon 11 of KIT, the juxtamembrane domain; this is the imatinib-sensitive majority in whom the drug turned a lethal sarcoma into a chronic disease.
- Subtypes: KIT exon 11 deletion (codons 557-558; higher risk); KIT exon 11 substitution or duplication (lower risk); Localised KIT exon 11-mutant GIST, high risk (three years of adjuvant imatinib); Metastatic KIT exon 11-mutant GIST on imatinib; Gastric versus small bowel KIT-mutant GIST
- Biomarkers: KIT exon 11 mutation type (deletion versus substitution); Mitotic count, size and site (Miettinen risk); KIT (CD117) and DOG1 immunohistochemistry; Secondary KIT mutations on progression (tissue or circulating tumour DNA); Imatinib plasma level in poor responders

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/gist-kit-exon-11/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/gist-kit-exon-11/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/gist-kit-exon-11/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/gist-kit-exon-11/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/gist-kit-exon-11/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/gist-kit-exon-11/#evidence [1 trial, 4 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/gist-kit-exon-11/#science [4 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/gist-kit-exon-11/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/gist-kit-exon-11/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/gist-kit-exon-11/coming/ [7 medicines, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/gist-kit-exon-11/data/ [33 connected records]

## Standard of care

- Localised, resectable: Complete surgical resection without lymphadenectomy; laparoscopic for smaller gastric tumours; neoadjuvant imatinib for large or poorly placed tumours. ([Imatinib](https://onco.cc/drugs/imatinib/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [KIT](https://onco.cc/targets/kit/))
- After resection, high risk: Three years of adjuvant imatinib 400 mg (SSG XVIII); trials of longer courses. ([Imatinib](https://onco.cc/drugs/imatinib/), [KIT](https://onco.cc/targets/kit/))
- Metastatic, first line: Imatinib 400 mg continued until progression, with CT response assessment by Choi criteria. ([Imatinib](https://onco.cc/drugs/imatinib/), [CT (computed tomography)](https://onco.cc/technologies/ct/), [KIT](https://onco.cc/targets/kit/))
- Progression on imatinib: Dose escalation to 800 mg, then sunitinib, regorafenib and ripretinib, ideally guided by the secondary mutation on circulating tumour DNA. ([Imatinib](https://onco.cc/drugs/imatinib/), [Sunitinib](https://onco.cc/drugs/sunitinib/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Ripretinib](https://onco.cc/drugs/ripretinib/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/))

## State of the art

- Imatinib in KIT-mutant GIST was the first targeted therapy for a solid tumour defined by its driver mutation and remains the model for the field.
- Three years of adjuvant imatinib is one of the few adjuvant targeted therapies proven to extend overall survival.
- Genotype now dictates dose and drug sequence, with circulating tumour DNA replacing repeat biopsy.

## Open problems

- Whether adjuvant imatinib should continue for five years or longer.
- Resistance through secondary KIT mutations in nearly every metastatic patient.
- Tumours that recur after stopping adjuvant therapy despite years of control.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor
- SSG XVIII (JAMA 2012): https://pubmed.ncbi.nlm.nih.gov/22453568/
- ACOSOG Z9001 (Lancet 2009): https://pubmed.ncbi.nlm.nih.gov/19303137/
- Wikipedia: https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor

## Connected records

- cancers: [Gastrointestinal stromal tumour (GIST)](https://onco.cc/cancers/gist/), [Imatinib-resistant GIST](https://onco.cc/cancers/gist-imatinib-resistant/), [PDGFRA D842V-mutant GIST](https://onco.cc/cancers/gist-pdgfra-d842v/)
- terms: [BAP1 loss](https://onco.cc/terms/bap1-loss/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria)](https://onco.cc/terms/gist-risk-stratification/)
- key papers: [Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumours](https://onco.cc/key-papers/paper-demetri-imatinib-gist-nejm-2002/), [Gain-of-function mutations of c-kit in human gastrointestinal stromal tumours](https://onco.cc/key-papers/paper-hirota-kit-gist-science-1998/), [Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumour](https://onco.cc/key-papers/paper-heinrich-kit-mutation-imatinib-response-jco-2003/), [SSG XVIII/AIO: one versus three years of adjuvant imatinib for operable gastrointestinal stromal tumour](https://onco.cc/key-papers/paper-ssg-xviii-adjuvant-imatinib-joensuu-jama-2012/)
- targets: [KIT](https://onco.cc/targets/kit/)
- drugs: [Bezuclastinib](https://onco.cc/drugs/bezuclastinib/), [IDRX-42](https://onco.cc/drugs/idrx-42/), [Imatinib](https://onco.cc/drugs/imatinib/), [NB003](https://onco.cc/drugs/nb003/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Ripretinib](https://onco.cc/drugs/ripretinib/), [Sunitinib](https://onco.cc/drugs/sunitinib/)
- technologies: [CT (computed tomography)](https://onco.cc/technologies/ct/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- trials: [INSIGHT](https://onco.cc/trials/insight-gist/)
- people: [Heikki Joensuu](https://onco.cc/people/heikki-joensuu/), [Michael C. Heinrich](https://onco.cc/people/michael-heinrich/)

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JSON: https://onco.cc/api/v1/entities/gist-kit-exon-11.json