Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population

• Published in: PloS one 2015-12, Vol.10 (12), p.e0144731-e0144731
• Main Authors: Ying, Jianming, Lin, Chen, Wu, Jian, Guo, Lei, Qiu, Tian, Ling, Yun, Shan, Ling, Zhou, Haitao, Zhao, Dongbing, Wang, Jian, Liang, Jianwei, Zhao, Jianjun, Jiao, Yuchen, Lu, Ning, Zhao, Hong
• Format: Article
• Language: English
• Subjects: Abdomen; Adult; Aged; ALK protein; Analysis; Asian Continental Ancestry Group - genetics; Automation; Biomarkers; Cancer; Cancer therapies; Chemotherapy; China; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Diagnosis; Digestive tract; DNA microarrays; DNA, Neoplasm - genetics; Enrichment; Epidermal growth factor; Esophageal Neoplasms - enzymology; Esophageal Neoplasms - genetics; Esophagus; Female; Fluorescence; Fluorescence in situ hybridization; Gastric cancer; Gastrointestinal tract; Gene fusion; Gene Rearrangement; Gene sequencing; Genes; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Incidence; Kinases; Laboratories; Lung cancer; Lung diseases; Lymphoma; Lymphomas; Male; Medical diagnosis; Membrane proteins; Metastasis; Middle Aged; Neoplasms, Squamous Cell - enzymology; Neoplasms, Squamous Cell - genetics; Oncology; Pathology; Patients; Physicians; Physiological aspects; Polymerase chain reaction; Protein-tyrosine kinase; Real-Time Polymerase Chain Reaction; Receptor Protein-Tyrosine Kinases - genetics; Spectrin; Squamous cell carcinoma; Stomach cancer; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Targeted Gene Repair - methods; Therapy; Tissue Array Analysis; Tumors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144731

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. 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. 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. 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.