ALK ALK FUSIONS Detail (hg19) (ALK)
Information
Genome
| Assembly | Position |
|---|---|
| hg19 | chr2:29,415,640-29,446,394 |
| hg38 | chr2:29,192,774-29,223,528 View the variant detail on this assembly version. |
Summary
MGeND
| Clinical significance | |
| Variant entry | |
| GWAS entry | |
| Disease area statistics | Show details |
ClinVar
| Clinical Significance | |
| Review star | [No Data.] |
| Show details | |
Disease area statistics
[No Data.]
MGeND
[No Data.]
ClinVar
[No Data.]
CIViC
| Disease | Drug | EL | ET | ED | CS | VO | TR | Pubmed | Links |
|---|---|---|---|---|---|---|---|---|---|
| lung non-small cell carcinoma | Ceritinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 26973324 | Detail |
| lung non-small cell carcinoma | Crizotinib | A |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 5 | 20979469 | Detail |
| lung non-small cell carcinoma | Crizotinib | A |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 5 | 23724913 | Detail |
| lung non-small cell carcinoma | Crizotinib | A |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 5 | 25470694 | Detail |
| lung non-small cell carcinoma | Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 24478318 | Detail |
| lung non-small cell carcinoma | Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 27022118 | Detail |
| lung non-small cell carcinoma | Retaspimycin Hydrochloride | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 2 | 20940188 | Detail |
| anaplastic large cell lymphoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 21345110 | Detail |
| inflammatory myofibroblastic tumor | Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 23598171 | Detail |
| diffuse large B-cell lymphoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 2 | 24330038 | Detail |
| lung non-small cell carcinoma | Alectinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 23639470 | Detail |
| lung non-small cell carcinoma | Alectinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 26938871 | Detail |
| lung non-small cell carcinoma | Alectinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 25153538 | Detail |
| lung non-small cell carcinoma | Alectinib | A |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 5 | 26708155 | Detail |
| colorectal adenocarcinoma | Crizotinib | E |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 1 | 19737969 | Detail |
| breast cancer | Crizotinib | E |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 1 | 19737969 | Detail |
| lung non-small cell carcinoma | Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 21933749 | Detail |
| lung non-small cell carcinoma | Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 26466010 | Detail |
| lung adenocarcinoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 25922291 | Detail |
| inflammatory myofibroblastic tumor | C |
Diagnostic
|
Supports
|
Positive | Somatic | 4 | 10383129 | Detail | |
| cancer | Entrectinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 28183697 | Detail |
| lung non-small cell carcinoma | Brigatinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 28475456 | Detail |
| lung non-small cell carcinoma | Alectinib,Crizotinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 5 | 28586279 | Detail |
| Anaplastic thyroid carcinoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 24687827 | Detail |
| vagina sarcoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 2 | 26942346 | Detail |
| epithelioid inflammatory myofibroblastic sarcoma | Crizotinib | C |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 2 | 25028698 | Detail |
| lung non-small cell carcinoma | Lorlatinib | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 4 | 30413378 | Detail |
| lung non-small cell carcinoma | Pemetrexed | B |
Predictive
|
Supports
|
Sensitivity/Response | Somatic | 3 | 21642865 | Detail |
DisGeNET
[No Data.]
Annotation
Annotations
| Descrption | Source | Links |
|---|---|---|
| Updated results from ASCEND-1 trial assessing safety and activity of ceritinib in ALK rearranged loc... | CIViC Evidence | Detail |
| In the Phase I study PROFILE 1001 (NCT00585195), a recommended crizotinib dose of 250 mg twice daily... | CIViC Evidence | Detail |
| This two arm Phase III study named PROFILE 1007 (NCT00932893) was performed to assess crizotinib vs.... | CIViC Evidence | Detail |
| This phase 3 trial named PROFILE 1014 (NCT01154140) compared crizotinib to established chemotherapy ... | CIViC Evidence | Detail |
| This retrospective study of patients from the PROFILE 1001 and 1005 studies of crizotinib in advance... | CIViC Evidence | Detail |
| This prospective Phase III study named Profile 1014 on NSCLC ALK-rearranged patients assessed intrac... | CIViC Evidence | Detail |
| In this study, heavily pretreated advanced NSCLC patients with various molecular tumor makeup were t... | CIViC Evidence | Detail |
| Crizotinib at 250mg daily was given to two patients with relapsed ALK-rearranged anaplastic large ce... | CIViC Evidence | Detail |
| As part of a phase 1 dose-escalation trial (NCT00939770), seven patients between ages 12 months and ... | CIViC Evidence | Detail |
| A 27 year old female patient with advanced-stage IV, CD20 negative diffuse large B cell lymphoma (DL... | CIViC Evidence | Detail |
| In this initial report of a single-arm Phase I and II study (JapicCTI-101264) of alectinib (CH542480... | CIViC Evidence | Detail |
| In this case study of a critically ill 29 year old male nonsmoker with advanced metastatic ALK-posit... | CIViC Evidence | Detail |
| In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in ... | CIViC Evidence | Detail |
| In this Phase II trial of 87 patients (NCT01871805), alectinib was assayed for safety and efficacy i... | CIViC Evidence | Detail |
| 26 colorectal adenocarcinoma samples were run on Affymetrix human Exon 1.0 arrays and a computationa... | CIViC Evidence | Detail |
| 84 breast cancer samples acquired from commercial sources were assayed on Affymetrix human exon 1.0 ... | CIViC Evidence | Detail |
| In a retrospective study comparing survival outcomes in a subgroup of 82 ALK-positive crizotinib-tre... | CIViC Evidence | Detail |
| A phase-3 clinical trial evaluated 347 patients with ALK-positive lung cancer. The study compared c... | CIViC Evidence | Detail |
| In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an EML4-ALK-E13;A20 rea... | CIViC Evidence | Detail |
| Fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 and immunohistochemist... | CIViC Evidence | Detail |
| Two phase I studies in patients with advanced or metastatic solid tumors, including patients with ac... | CIViC Evidence | Detail |
| In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-... | CIViC Evidence | Detail |
| In a randomized, open-label phase 3 trial 303 patients with ALK-positive, previously untreated NSCLC... | CIViC Evidence | Detail |
| A patient with anaplastic thyroid carcinoma harboring ALK rearrangement received crizotinib after ch... | CIViC Evidence | Detail |
| Patient was 34-year-old woman with vaginal sarcoma, which was excised with positive surgical margins... | CIViC Evidence | Detail |
| This is a case report of a 22-year-old Japanese man with a pelvic mesenchymal neoplasm. Tumor analy... | CIViC Evidence | Detail |
| In a phase 2 trial, patients with NSCLC with ALK fusion received lorlatinib. In treatment-naive pati... | CIViC Evidence | Detail |
| Among 95 patients with NSCLC in this study, 15 had an ALK translocation. ORR of these patients compa... | CIViC Evidence | Detail |
- Gene
- ALK
- Genome
- hg19
- Position
- chr2:29,415,640-29,446,394
- Variant Type
- fusion
- Variant (CIViC) (CIViC Variant)
- ALK FUSIONS
- Transcript 1 (CIViC Variant)
- ENST00000389048.3
- Variant URL (CIViC Variant)
- https://civic.genome.wustl.edu/links/variants/499
- Summary (CIViC Variant)
- Following the initial discovery and characterization of NPM-ALK fusion mutation in anaplastic large cell lymphoma (ALCL), EML4-ALK fusions were found to be driver mutations in a subset of lung adenocarcinomas. ALK fusions bring the C-terminal ALK kinase domain together with the N terminal region of the fusion partner, and have since been found in a range of cancers including inflammatory myofibroblastic tumor, renal cell carcinoma, diffuse large B cell lymphoma and colorectal cancer. In a Phase I trial for crizotinib, a 92% response rate was seen in the subset of patients with a specific EML4-ALK variant, which was higher than the 57% rate in the overall ALK-rearranged population, but the subpopulation numbers were insufficient to correlate variant type with patient response. Due to restricted wild-type ALK expression, and also mild phenotypes seen in ALK knockout mice, ALK fusions are desirable targets. ALK inhibitor TAE684 was used in initial characterizations of ALK fusion cancer drivers, and crizotinib – a small molecule ATP-competitor RTK inhibitor which is highly selective for ALK and MET - has been approved as first line therapy in ALK-rearranged NSCLC. ALK-rearrangement defines an NSCLC subtype that makes up 3-5% of NSCLC cases, and is characterized by higher proportions of younger patients and never smokers. EML4-ALK variant 1 is the most common ALK fusion in NSCLC and was the first to be discovered and demonstrate cancer driver properties in vitro and in mouse models. A Phase I study of crizotinib in ALK-rearranged NSCLC demonstrated an increase in overall survival when compared to standard chemotherapy. These and other initial results prompted accelerated approval for crizotinib in NSCLC. Continued clinical work demonstrated benefit with crizotinib over chemotherapy in multi-armed studies, and as first line therapy. Crizotinib was also found to remain beneficial to NSCLC patients who had progressed on crizotinib. Additionally, crizotinib was shown to increase intracranial disease control in brain metastasis occurring from ALK-rearranged NSCLC.
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