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Series GSE42109 Query DataSets for GSE42109
Status Public on Jan 30, 2013
Title Identification of anaplastic lymphoma kinase as a candidate of new therapeutic target for BCC
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background; Basal cell carcinoma (BCC) is the most common cancer in humans. The pathogenesis of BCC is associated with the sonic hedgehog (SHH) signaling pathway. Vismodegib, a smoothened inhibitor, that targets this pathway is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. Methods; We studied gene expression profiling of BCC tumour tissue coupled with laser capture microdissection to identify tumor specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. The expression of selected molecules was confirmed by quantitative RT-PCR (qRT-PCR) and by immunohistochemistry. The action of kinase inhibitors was examined on primary normal human epidermal keratinocytes. Results; We found a >250 fold change increase (false discovery rate <10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger staining of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Additionally, Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met, another receptor tyrosine kinase, inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 mRNA by approximately 60% and 20%, respectively (p<0.05). Conclusions; Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promotes keratinocyte proliferation. Furthermore, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients.
Overall design Laser capture microdissection was performed on 5 cases of nodular/superficial BCC, 5 cases of infiltrative BCC.
Contributor(s) Mitsui H, Ning H, Suárez-Fariñas M, Krueger JG
Citation(s) 24163262
Submission date Nov 07, 2012
Last update date Mar 25, 2019
Contact name Mayte Suarez-Farinas
Organization name Mount SinaiSchool of Medicine
Street address 1425 Madison Ave, L2-70C, Box 1077,
City New York
State/province NY
ZIP/Postal code 10075
Country USA
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (21)
GSM1032610 BCC371 TM/EPI
GSM1032611 BCC371 TM/D
GSM1032612 BCC368 TM
BioProject PRJNA179149

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Supplementary file Size Download File type/resource
GSE42109_RAW.tar 65.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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