Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement Detection Using Fluorescene In-Situ Hybridization (FISH) In Lung Cancer Prognostication

ABSTRACT

Lung cancer is a leading cause of cancer related death worldwide. It is increasing at a very fast rate in both men and women. Some significant mutations occurring at molecular level in lung adenocarcinoma, like ALK, EGFR, KRAS, MET, and, ALK (anaplastic lymphoma kinase) gene mutations for an ALK encoded transmembrane receptor tyrosine kinase domain and subsequently participating in the progression of Non-Small Cell Lung Adenocarcinoma (NSCLC). Some fusion partner genes involved in this process are EML-4, KLC1, KIF5B and TFG. The ALK-EML-4 rearrangement is the second most common oncogenic mutation in the nonsmall cell lung adenocarcinoma. There is 3-7% ALK mutation occurring in early or never-smokers in accompanying NSCLC. The NSCLC with ALK gene mutation generally do not have EGFR or KRAS gene mutation which are also molecular markers, which get mutated in cancer. For the detection of ALK mutation in NSCLC, different types of techniques like Fluorescence in situ Hybridization (FISH), Immunohistochemistry (IHC) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) are being used. On the basis of sensitivity and specificity, FISH is gold standard in detecting the mutation when compared with other methodologies like IHC and RT- PCR. However in the Indian setting, FISH is more expensive and hence not available everywhere. In this review the efficacy of these different techniques in detecting ALK mutation and the detailed interpretation of results obtained with FISH has been discussed. For the treatment of ALK/MET mutated NSCLC patients an orally administered drug, crizotinib drug (tyrosine kinase inhibitor) has been approved by Food and Drug Administration (FDA) of United States. Highly sensitive and specific techniques are used for the detection of ALK gene mutation in NSCLC patients which have to be given for crizotinib treatment.