The invention relates to the use of high-density loss of heterozygosity (LOH) mapping in lung adenocarcinoma to identify intragenic LOH and driver mutations in different domains of ALK resulted in enhanced tumor growth in xenografted mouse. Mutant (H694R and E1384K) ALKs shows activation of Y1604 ALK and downstream Akt, STAT3 and ERK signaling pathways. Increases of oncogenic signalings result in enhancing cell proliferation, colony-formation, cell-migration and tumor-growth in xenografted mouse. Western blot and immunohistochemistry analysis using antibody against phospho-Y1604 ALK on 11 lung cancer cell-lines and 263 cancer specimens indicates ALK activation in all lung cancers regardless of tumor stages. Treating mutant-bearing mice with ALK inhibitor WHI-P154 results in tumor shrinkage, metastasis suppression and improving survival. Hyperphosphorylation of Y1604 ALK occurs early and continuously throughout tumor progression and can be used as a biomarker to detect lung cancer. Oncogenic ALK point mutations can be treatment targets for lung cancer.本發明係關於利用肺腺癌中高度的對偶基因失落(LOH)圖譜以發現高頻率基因內LOH及異生性淋巴瘤激酶不同區域中之不同突變型所導致異體移植老鼠腫瘤生長被強化之情形。異生性淋巴瘤激酶之突變型(H694R及E1384K突變型)加強第1604位置酪胺酸之磷酸化並活化異生性淋巴瘤激酶及其下游之Akt、STAT3及ERK致癌訊號傳遞途徑。在異體移植的老鼠體內，致癌訊號之增加導致強化了細胞增生、細胞群落形成、細胞遷移以及腫瘤的生長。利用西方墨點法及免疫組織化學染色分析，透過抗體偵測11株肺癌細胞株及263個癌組織樣本中第1604位置之酪胺酸具有磷酸化之異生性淋巴瘤激酶，證實不論處於何種癌症時期，所有的肺癌中之異生性淋巴瘤激酶均被活化。以異生性淋巴瘤激酶抑制劑WHI-P154治療突變鼠能導致腫瘤萎縮、抑制轉移並增進存活。異生性淋巴瘤激酶位於胺基酸序列第1604位置之酪胺酸被高度磷酸化會導致提早且持續性地使腫瘤惡化，而異生性淋巴瘤激酶位於胺基酸序列第1604位置之酪胺酸被高度磷酸化能作為用於檢測肺癌之生物指標。致癌化之點突變的異生性淋巴瘤激酶能做為治療肺癌之標的。
