EML4-ALK is the only driving mutation of non-small cell lung cancer.
In 2007, two independent research groups found ALK gene rearrangement in non-small cell lung cancer.
A group of researchers developed a retroviral cDNA expression library for screening new oncogenes. They transfected the cDNA library of lung adenocarcinoma extracted from a 62-year-old Japanese male smoker, who had negative mutations in KRAS and EGFR. They designed and produced transgenic mice, which specifically expressed EML4-ALK in alveolar cells, thus producing many lung adenocarcinoma nodules. Compared with untreated mice, treating these transgenic mice with ALK inhibitors resulted in a decrease in tumor load. Most mice died within 1 month. Treatment with the same ALK inhibitor resulted in no infiltration of EML4-ALK/3T3 cells in the lung and prolonged the survival time. This study strongly confirmed that EML4-ALK is the only driving mutation in non-small cell lung cancer, and inhibiting the activity of EML4-ALK in vivo will lead to the reduction of lung cancer load.
The product of ALK fusion gene is a fusion tumor protein with a molecular weight of 80 kD, and its ability to transform cells has been recognized. P80NPM-ALK significantly increased the proliferation rate by making rat fibroblasts grow in a way independent of adhesion. In addition, it can also transform Ba/F3 cells into IL? 3 don't rely on it. NPM-ALK was transfected into bone marrow cells of mice by retrovirus, and these mice developed T cell and B cell large cell lymphoma.
Although P80npm-ALK is concentrated in the nucleus due to the unique function of npm, it is not necessary for NPM to transform ALK, because it is found that other genes can be fused with ALK gene to activate ALK. Although these tumor proteins are not concentrated in the nucleus, cells can still undergo malignant transformation. This discovery is completely consistent with some clinical phenomena: a variety of chromosome translocation involving ALK gene can cause structural activation of ALK and cause ALCL. Therefore, this group of diseases is also called ALK positive lymphoma or ALKoma.
Identification of "kinesin" in non-small cell lung cancer
At the same time, another group of researchers identified the characteristics of phosphorylated tyrosine in 1, 9 1 cell lines and tumor samples of non-small cell lung cancer, thus determining that ALK is a "driving kinase" in non-small cell lung cancer.
Therefore, two different methods were used to determine ALK translocation in the two groups, which is the first time in common malignant solid tumors.