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Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

ABSTRACT: We collected ALK-positive patients with advanced NSCLC retrospectively and studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling was detected among these patients. This project includes the DNA-seq raw data of 64 patients and RNA-seq raw data of 3 patients enrolled in the study.

SUBMITTER: Xian,Zhang

PROVIDER: OEX010803 | NODE |

REPOSITORIES: NODE

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Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

Project description:We collected ALK-positive patients with advanced NSCLC retrospectively and studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling was detected among these patients. This project includes the DNA-seq raw data of 64 patients and RNA-seq raw data of 3 patients enrolled in the study.

| OEX010805 | NODE

Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

| OEX010804 | NODE

Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

| OEX010802 | NODE

Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

| OEX010806 | NODE

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer.

Project description:BackgroundEchinoderm microtubule-associated protein-like 4 (EML4) is the canonical anaplastic lymphoma kinase (ALK) fusion partner in non-small cell lung cancer (NSCLC), and ALK-positive patients showed promising responses to ALK tyrosine kinase inhibitors (TKIs). However, studies that comprehensively investigate ALK TKI treatment in patients with different ALK fusion patterns are still lacking.MethodsNinety-eight ALK-positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling (CGP) was conducted to divide patients into different groups based on their ALK fusion patterns. Non-canonical ALK fusions were validated using RNA-sequencing.Results54.1% of patients had pure canonical EML4-ALK fusions, 19.4% carried only non-canonical ALK fusions, and 26.5% harbored complex ALK fusions with coexisting canonical and non-canonical ALK fusions. The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex ALK fusion group. Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010). The complex ALK fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies. Most identified non-canonical ALK fusions were likely to be expressed in tumors, and some of them formed canonical EML4-ALK transcripts during mRNA maturation.ConclusionOur results suggest NSCLC patients with complex ALK fusions could potentially have better treatment outcomes to ALK TKIs therapy. Also, diagnosis using CGP is of great value to identify novel ALK fusions and predict prognosis.

| S-EPMC7759679 | biostudies-literature

Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

| OEX010794 | NODE

Complex ALK fusions are associated with better prognosis in advanced non-small cell lung cancer

| OEX010793 | NODE

ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms.

Project description:Oncogenic ALK fusions occur in several types of cancer and can be effectively treated with ALK inhibitors; however, ALK fusions and treatment response have not been characterized in malignant melanomas. Recently, a novel isoform of ALK (ALKATI ) was reported in 11% of melanomas but the response of melanomas expressing ALKATI to ALK inhibition has not been well characterized. We analyzed 45 melanoma patient-derived xenograft models for ALK mRNA and protein expression. ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas express wild-type (wt) ALK and/or ALKATI and one mucosal melanoma expresses multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK variants were tested for response to ALK inhibitors. Whereas the melanoma expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo, the melanomas expressing wt ALK or ALKATI were not sensitive to ALK inhibitors. In addition, a patient with mucosal melanoma expressing ALKATI was treated with an ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our results demonstrate ALK fusions occur in malignant melanomas and respond to targeted therapy, whereas melanomas expressing ALKATI do not respond to ALK inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset of melanoma patients, but additional clinical studies are needed to determine the efficacy of targeted therapies in melanomas expressing wt ALK or ALKATIMol Cancer Ther; 17(1); 222-31. ©2017 AACR.

| S-EPMC5752582 | biostudies-literature

Infant high grade gliomas comprise multiple subgroups characterised by novel targetable gene fusions and better survival

Project description:Methylation array profiling of infant high grade gliomas identifies an intrinsic group of tumours with epigenetic profiles distinct from gliomas in older children. These tumours are characterised by very few recurrent mutations and carry a very high frequency of fusion genes. They can be diagnosed according to their methylation profile and novel treatments are available targeting the different fusion genes.

2019-08-09 | E-MTAB-7802 | biostudies-arrayexpress

Infant high grade gliomas comprise multiple subgroups characterised by novel targetable gene fusions and better survival

2019-08-12 | E-MTAB-7804 | biostudies-arrayexpress

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