期刊
MOLECULAR DIAGNOSIS & THERAPY
卷 23, 期 3, 页码 395-405出版社
ADIS INT LTD
DOI: 10.1007/s40291-019-00389-y
关键词
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资金
- Shanghai Municipal Commission of Health and Family Planning [2018ZHYL0213]
- Interdisciplinary Program of Shanghai Jiao Tong University [ZH2018QNA66]
- Shanghai Chest Hospital Projects for Development of Science and Technology [YZ2015-ZX]
BackgroundThe clinicopathological features and genomic rearrangements of anaplastic lymphoma kinase (ALK) fusion cases have not been fully identified.ObjectiveOur objective was to explore the status of ALK in non-small-cell lung cancer (NSCLC) specimens, to explore the relationships between ALK status and clinicopathological features and to identify genomic rearrangements via capture-based next-generation sequencing (NGS).MethodsWe tested 9889 NSCLC specimens for ALK status using the Ventana anti-ALK (D5F3) antibody. Clinicopathological features were analyzed and genomic rearrangements identified using capture-based NGS in 76 ALK-positive cases.ResultsIn total, 485 specimens (4.90%) tested positive for ALK. The positivity rate was higher for adenocarcinoma samples than for non-adenocarcinoma samples (6.03 vs. 1.47%; p<0.001) and for biopsies/cell blocks than for surgical specimens (7.00 vs. 4.16%; p<0.001). Patient age, patient sex, specimen type, specimen histotype, and patient smoking history were all significantly correlated with ALK status. Genomic rearrangements were detected in 98.68% (75/76) of the ALK-positive samples; 89.33% (67/75) carried the canonical EML4-ALK, and the remaining samples carried only noncanonical ALK rearrangements. Four of these noncanonical ALK fusion samples were identified as carrying EML4-ALK transcripts at the RNA level. A novel fusion variant, SRD5A2-ALK, was revealed.ConclusionsYounger patients with NSCLC, especially those aged<30years, were more likely to test positive for ALK. Positive ALK test results were more common in patients with invasive mucinous adenocarcinoma and solid-predominant invasive adenocarcinoma than in patients with other histotypes. Samples that carried only noncanonical ALK rearrangements may also have carried the canonical EML4-ALK, which was not detected by capture-based NGS. EML4-ALK transcripts might result from rare splicing mechanisms without genomic rearrangements.
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