Mutated genes in cancer (2) – EML4

EML4

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 27436 or EML4

● Ensembl (http://www.ensembl.org/index.html): ENSG00000143924

● UniProt (http://www.uniprot.org/): Q9HC35

● OMIM (http://www.ncbi.nlm.nih.gov/omim): 607442

● GeneCards (http://www.genecards.org/): EML4

● HGNC (http://www.genenames.org/): 1316 or EML4

Gene locus:

2p21

Protein name:

Echinoderm microtubule associated protein like 4

Protein Size:

981 amino acids; about 109 kDa

Function:

Strongly overexpressed during mitosis, EML4 is necessary for correct microtubule  formation.

Cancer-related alterations:

EML4 is involved in fusions with ALK (inv(2)(p21p23)) in non-small cell lung carcinoma (NSCLC). EML4-ALK fusion transcript is detectable in a low amount (frequency between 2,7% and 6,7%) of NSCLC-samples and NSCLC-cell-lines. EML4-ALK is a protein tyrosine kinase, which is constitutively dimerized and thus activated.

Therapy:

Alk-inhibitors impede proliferation in EML4-ALK-fusion positive lung cancer cell-lines. In experiments with transgenic mice, treatment with ALK-inhibitors resulted in reduced tumor mass. The EML4-ALK fusion gene was identified as a potentially targetable oncogenic driver in non-small cell lung cancer in 2007. A small molecule ALK inhibitor, crizotinib, may now be on the verge of approval by the FDA for the treatment of ALK-rearranged lung cancer (Gerber DE, Minna JD 2010).

References (free access):

ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Gerber DE, Minna JD. Cancer Cell. 2010 Dec 14;18(6):548-51.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110762/pdf/nihms295249.pdf

EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H; ALK Lung Cancer Study Group. N Engl J Med. 2010 Oct 28;363(18):1734-9.

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1007478

The biology and treatment of EML4-ALK non-small cell lung cancer. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA. Eur J Cancer. 2010 Jul;46(10):1773-80.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888755/pdf/nihms195408.pdf