# ALK fusion (ALK-positive)

Source: https://onco.cc/biomarkers/alk-fusion/  
OnCo record `alk-fusion` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An ALK fusion, usually EML4::ALK, is a swapped piece of chromosome 2 that turns the ALK kinase on permanently in about 4 percent of lung adenocarcinomas. Seven ALK inhibitors are approved for it, including alectinib after surgery.

## Summary

ALK rearrangements are detected by break-apart FISH (Vysis), immunohistochemistry (Ventana D5F3), or DNA and RNA sequencing; the FDA list carries all three routes as companion diagnostics. Crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and ensartinib are labelled for ALK-positive metastatic NSCLC 'as detected by an FDA-approved test', and alectinib for adjuvant treatment after resection of tumours 4 cm or larger or node-positive (ALINA). Crizotinib is also labelled for ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumour. Alectinib's label allows selection on tumour tissue or plasma.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: ALK fusion; ALK rearrangement; ALK-positive; ALK+; EML4-ALK; EML4::ALK; ALK translocation; ALK gene rearrangement
- Tags: biomarker; fusion

## Notes

- Pancreatic ductal adenocarcinoma: ALK fusions in 0.16% of 3,170 tumours, all KRAS wild-type and all in patients under 50 (1.3% of that age group), with benefit from ALK inhibitors in 3 of 4 treated (Singhi 2017).
- Lung cancer: 3 to 6% of adenocarcinomas by panel and 8% by fluorescence in situ hybridisation in the Lung Cancer Mutation Consortium, with EML4 the partner in the large majority (Soda 2007, Kris 2014; cBioPortal). Immunohistochemistry is an acceptable screen and a DNA panel that does not bait the breakpoint introns will read wild-type (Lindeman 2018). At progression the gene is read again for resistance mutations, which decide whether a third-generation inhibitor is the right next step (Gainor 2016, Shaw 2019).

## Sources

- ALECENSA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42c49deb-713b-427a-9670-08af08adcffb
- Lorbrena prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=004f93d7-a1cd-4b67-9207-31cdcb5c5976

## Connected records

- biomarkers: [ALK kinase-domain resistance mutation (G1202R and the rest)](https://onco.cc/biomarkers/alk-resistance-mutation/), [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/), [RET fusion and RET mutation](https://onco.cc/biomarkers/ret-fusion/), [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)
- cancers: [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Alectinib](https://onco.cc/drugs/alectinib/), [Brigatinib](https://onco.cc/drugs/brigatinib/), [Ceritinib](https://onco.cc/drugs/ceritinib/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Ensartinib](https://onco.cc/drugs/ensartinib/), [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/), [Lorlatinib](https://onco.cc/drugs/lorlatinib/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene fusion](https://onco.cc/terms/gene-fusion/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- key papers: [ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/), [Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-singhi-alk-rearrangements-pancreatic-jnccn-2017/), [Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer](https://onco.cc/key-papers/paper-soda-eml4-alk-fusion-nature-2007/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/), [Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer](https://onco.cc/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/), [Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F](https://onco.cc/key-papers/paper-shaw-alk-l1198f-resensitisation-nejm-2016/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/)
- targets: [ALK](https://onco.cc/targets/alk/)

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