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Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese
Jianming Ying1, Chen Lin2, Jian Wu3
1Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
Background:
Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.
Patients And Methods:
Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
Results:
Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
Conclusions:
The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.
Insights
Anaplastic lymphoma kinase (ALK) gene fusions were detected in 0.44% of Chinese colorectal cancer (CRC) patients. A novel SPTBN1-ALK fusion was identified, offering potential new targets for anti-ALK therapy in CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) rearrangements are key in specific lung cancers, enabling targeted therapy.
- Digestive tract cancers encompass esophageal, gastric, and colorectal cancers (CRC).
Purpose of the Study:
- To determine the incidence of ALK gene fusions in a large cohort of Chinese patients with digestive tract cancers.
- To identify novel ALK fusion partners in these cancers.
Main Methods:
- Tissue microarrays from 808 patients (esophageal, gastric, CRC) were analyzed.
- Immunohistochemistry (IHC) for ALK expression, followed by fluorescence in situ hybridization (FISH), qRT-PCR, and sequencing for fusion confirmation.
Main Results:
- Two (0.44%) colorectal cancer (CRC) cases showed positive ALK expression by IHC and FISH.
- One CRC case had an EML4-ALK fusion; another had a novel SPTBN1-ALK fusion.
- No ALK fusions were detected in gastric or esophageal cancers, though one gastric case had partial IHC positivity.
Conclusions:
- The incidence of ALK gene fusion in Chinese CRC patients is 0.44%.
- ALK fusions were not detected in Chinese gastric or esophageal cancer patients.
- The novel SPTBN1-ALK fusion presents a potential therapeutic target for anti-ALK treatments.
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