"Diamond mutation" ALK gene diagnosis

Recently, Pfizer announced that the world’s first third-generation ALK inhibitor, Lorbrena® (generic name: Lorlatinib Tablets), has been approved by the State Drug Administration as a single drug for anaplastic lymphoma Treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) positive for kinase (ALK). This is also the first approved third-generation ALK inhibitor in China.

Introduction to ALK Gene

ALK was first discovered in a subtype of anaplastic large cell lymphoma (ALCL), hence the name anaplastic lymphoma kinase (ALK). Subsequently, before the discovery of ALK gene rearrangement in non-small cell lung cancer, multiple types of ALK gene rearrangement were found in diffuse large B-cell lymphoma and inflammatory myofibroblastic tumor (IMT), respectively. ALK is a potent oncogenic driver gene.

An important clinical subtype of non-small cell lung cancer (NSCLC) is ALK gene fusion, mainly EML4-ALK fusion mutation, EML4-ALK fusion has different fusion subtypes. Common isoforms of EML4-ALK fusions: v1, v2, v3a, v3b, v4, v5a, v5b, v6, v7.

The incidence of anaplastic lymphoma kinase (ALK) gene fusion in non-small cell lung cancer in my country is about 5.6%, and the incidence of adenocarcinoma is 6.6%-9.6%. The reason why ALK mutation is called "diamond mutation" is because its mutation frequency is not high, and ALK+ patients are as rare as diamonds; There is a good response to drug treatment. Of course it is unfortunate to suffer from cancer, but having ALK+ is a "fortunate" among misfortunes.

ALK detection method

It is of great clinical significance to select an accurate, rapid and appropriate ALK detection method and to screen out the target population suitable for ALK inhibitors. At present, the main detection methods for ALK mutations at home and abroad include fluorescence in situ hybridization (FISH), immunohistochemical staining (IHC), fluorescence quantitative PCR (RT-PCR) and next-generation sequencing (NGS).

Indoor and outdoor quality control of ALK detection

1. The testing laboratory should establish and optimize the standardized operation process of ALK testing before clinical application, and conduct necessary performance verification.

2. Testing laboratories should regularly participate in ALK testing inter-laboratory quality assessment activities, at least twice a year.

3. Testing laboratories should set negative and positive controls.

4. The testing laboratory should designate a special person to be responsible for the quality control of ALK gene testing, and regularly organize personnel comparison, training, and data summary and analysis.

We can provide diagnostic standards for various types of ALK mutations to ensure the detection limit, sensitivity and stability of the diagnostic method.

ALK p.F1174L Reference Standard RQP10225

AI-Edigene® EML4(E6)-ALK (E20) V3a Fusion RQP20184R

AI-Edigene® EML4(E6)-ALK (E20) V3b  Fusion RQP20185R

AI-Edigene® EML4(E18)-ALK (E20) v1 Fusion RQP20169R

AI-Edigene® EML4(E20)-ALK (E20) Fusion RQP20168R

EML4(E13)-ALK(E20) Fusion RQP20020R

NPM1-ALK Fusion RQP20032R

ALK-PTPN3 Fusion RQP20073R