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ALK G1202R
GeneALK
Variantmissense
Amino Acid ChangeG1202R
DNA Change (Coding Nucleotide)3604G>A
Transcript ID (GRCh37/hg19)ENST00000389048
Codon1202
Exon23
Genomic Coordinates (GRCh37/hg19)2:29443613-29443613
COSMIC ID144250
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
See All Pertinent Negatives

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Tier 2
ALK
Variants
ALK G1202R
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung Carcinoma
Interpretation

The anaplastic lymphoma kinase (ALK) has emerged as a potentially relevant biomarker and therapeutic target in a variety of solid and hematologic malignancies. It is a receptor tyrosine kinase (RTK) that is known to be activated either by point mutations or by chromosomal translocations. These genetic alterations act as oncogenic drivers, promoting constitutive, ligand-independent activation of this RTK. Approximately 3-7% of non-small cell lung cancers (NSCLC) harbor ALK fusions/rearrangements. ALK fusion oncogenes are transforming both in vitro and in vivo, defining a distinct clinicopathologic subset of NSCLC that are highly sensitive to therapy with ALK-targeted inhibitors. While crizotinib (ALK/MET TKI) is highly active in patients with ALK-positive NSCLC, patients have been shown to invariably develop resistance to this drug. In approximately one-third of resistant cases, tumors can acquire a secondary mutation within the ALK tyrosine kinase domain. ALK G1202R is postulated to be in the solvent-exposed region abutting the crizotinib-binding site, likely diminishing the binding affinity of crizotinib and other ALK inhibitors to the mutant ALK. G1202R has been shown to cause resistance to crizotinib as well as second generation ALK inhibitors (ceritinib, alectinib).

Last updated: 2020-07-24 14:53:15 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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