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Alk B pyrosequencing

ABSTRACT: Alk B pyrosequencing -Secondary successional trajectories of structural and catabolic bacterial communities in oil-polluted soil planted with hybrid Poplar

PROVIDER: PRJEB7645 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR664671.fastq.gz	Fastqsanger.gz
	ERR664672.fastq.gz	Fastqsanger.gz
	ERR664673.fastq.gz	Fastqsanger.gz
	ERR664674.fastq.gz	Fastqsanger.gz
	ERR664675.fastq.gz	Fastqsanger.gz

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Project description:Extradiol dioxygenase pyrosequencing- Secondary successional trajectories of structural and catabolic bacterial communities in oil-polluted soil planted with hybrid Poplar

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Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels.

Project description:High anaplastic lymphoma kinase (ALK) protein levels may be correlated with an unfavorable prognosis in neuroblastoma (NBL) patients, regardless of ALK mutation status. We therefore examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated (MUT) and wild type (WT) NBL cell lines. Six of the nineteen NBL cell lines had a point mutation and four an amplification of the ALK gene. ALK amplified cell lines showed similar ALK levels and ALK inhibitor sensitivity as WT cell lines and were therefore co-analyzed. The ALK mRNA (p=0.043), ALK 220 kDa (p=0.009) and ALK 140 kDa (p=0.025) protein levels were higher in ALK mutant (n=6) than WT cell lines (n=13). ALK mRNA and protein levels significantly correlated with ERK1 and ERK2 protein levels, and also with PHOX2B mRNA levels, a neural differentiation marker which is mutated in NBL. Response to ALK inhibitor TAE684 was also significantly correlated with ALK levels. ALK mutant cell lines (n=4) demonstrated a higher sensitivity towards ALK inhibitor TAE684 (14.9 fold more sensitive, p=0.004) than eight WT cell lines. These results underline the importance of ALK mutations but also ALK levels for response to ALK inhibitors in NBL cell lines. Furthermore, the strong correlation of PHOX2B and ALK suggests that neural differentiation stage may be correlated with ALK levels in neuroblastoma. These data will enhance understanding of ALK inhibitor response in future patient trials.

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Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels.

2011-07-07 | E-GEOD-22771 | biostudies-arrayexpress

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Project description:Starting with H3122 cells, which harbor the EML4-ALK E13;A20 fusion and are known to be sensitive to ALK tyrosine kinase inhibitors, we generated isogenic pairs of ALK TKI sensitive and ALK TKI resistant cell lines using established methods (see Chmeliecki, J et al Science Trans Med 2011). We modeled resistance against the currently FDA approved ALK TKI, crizotinib (also called PF-1066). We also modeled resistance against a novel more potent ALK inhibitor, X-376 (ref: Lovly, CM et al Cancer Research 2011). We compared gene expression profiles between the 'parental' (ALK TKI sensitive) H3122 cells and the drug resistant cells (H3122 CR for Crizotinib resistant cells and H3122 XR for X-376 resistant cells).

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