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Molecular Genetics of Lung AdenoCA : ALK

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ALK translocations: About 3-5% of lung adenocarcinomas harbor translocations involving the ALK gene. ALK fusions are more commonly seen in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor; however EML4-ALK fusion is almost exclusively seen in lung adenocarcinomas.

Features of ALK-translocated lung adenocarcinomas: No linkage to smoking (never-smokers or light smokers), younger age group (about 10 yrs. younger than ALK-negative tumors), and no mutations in EGFR, KRAS, and TP53 genes. The tumors have solid, acinar or cribriform morphology with prominent mucin production often with signet ring cell appearance. The ALK protein levels are low and may be false-negative by immunohistochemistry.

Targeted Therapy: Several inhibitors of ALK tyrosine kinase have become available as a targeted therapy for this small group of lung adenocarcinoma patients. They include Crizotinib (Xalkori), Certinib (Zykadia), and Alectinib (Alecensa).

The image shows acinar type of lung adenocarcinoma.

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