What are the Uncommon Anaplastic Lymphoma Kinase (ALK) Fusions in Non-Small Cell Lung Cancer?

The lung cancer carcinogenesis is increasingly related to genetic disorders that lead to use specific targeted therapies which improve clinical outcome and survival. Gene fusion is one of the mechanisms of lung cancer pathogenesis besides gene mutation. The oncogenic echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was the first described in non small cell lung cancer (NSCLC) and it’s the most frequent ALK rearrangement which occurs in approximately 5% of NSCLC. The development of sequencing technology has allowed the discovery of other ALK partners that cause an ALK fusion in NSCLC. They are still less known, however. The aim of this revue is to report the novel ALK fusions in NSCLC described in the literature and their particular characteristics. We will present the kinesin family member 5B (KIF5B) - ALK fusion, the huntingtin interacting protein 1 (HIP 1)- ALK fusion, and other uncommon ALK fusions.

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Detection of Anaplastic Lymphoma Kinase (ALK) gene in Non-Small Cell lung Cancer (NSCLC) By CISH Technique

Cancer and Clinical Oncology ◽

10.5539/cco.v7n1p22 ◽

2018 ◽

Vol 7 (1) ◽

pp. 22

Author(s):

Mohanad Ali AlBayyaa ◽

Ban A. Abdulmajeed

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Anaplastic Lymphoma Kinase ◽

Gene Rearrangement ◽

Small Cell ◽

Small Cell Lung ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Signal Pattern

Background/Aim: Anaplastic Lymphoma Kinase (ALK) rearrangement has evaluated activity of NSCLC compared with other molecular subtypes (EGFR, KRAS). Many studies demonstrated that patients with ALK rearrangement positive NSCLC have improved with a good response rates and progression (free survival) when treated with either monotherapy or by a combination therapy compared with EGFR-mutated, KRAS/EGFR/ALK wild type or KRAS-mutated. The aim of this study was to detect and study the signal pattern of normal ALK and compare it to that of mutated ALK with gene rearrangement in cases of non-small cell lung cancer and Inflammatory conditions by implementing the CISH technique. In addition to correlate ALK signal pattern with the histopathological type and grade as well as the age and sex of the patients.Materials & Methods: Forty patients with NSCLC and Inflammatory diseases were enrolled in a comparative cross sectional study. The tissue blocks were sectioned on non-charged slides for the preparation of routine H&E staining. Positively charged slides were used for tissue sections prepared for chromogenic in situ hybridization procedure to detect ALK gene.Results: ALK gene signal break apart was detected in (18/20, 90%) of malignant cases; (0/20, 0%) of non-neoplastic lung lesions. There was a significant statistical difference in their distribution, p < 0.05. While There was no significant association between any disease status and sex P value = 1.000NS. The CISH test was 100% sensitive using negative score as a cutoff point and 90.9% specific. The score was divided into three levels that categorized the cases, so there were six cases in score one (1-32%), nine cases in score two (33-67%) and three cases in score three (68-100%).Conclusion: Detection of ALK rearrangement in the early diagnosis of NSCLC is highly sensitive and can save a lot of efforts in planning chemotherapy regimens. Results were very promising in identifying this mutation by a sensitive and highly specific test. The ALK gene rearrangement could be an early mutation and it is needed as an initiating step for the carcinogenesis process. The presence of a double gene mutation, however, could be the cause of a higher-grade cancer.

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