Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|Authors||Dabir S, Babakoohi S, Kluge A, Morrow JJ, Kresak A, Yang M, MacPherson D, Wildey G, Dowlati A|
|Title||RET mutation and expression in small-cell lung cancer.|
|Journal||Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer|
|Abstract Text||There is growing interest in defining the somatic mutations associated with small-cell lung cancer (SCLC). Unfortunately, a serious blockade to genomic analyses of this disease is a limited access to tumors because surgery is rarely performed. We used our clinical/pathologic database of SCLC patients to determine the availability of biopsy specimens that could be used for genomic studies and to identify tumors for initial oncogene analysis.DNA was extracted from six tumors, three primary and three metastatic, and analyzed by SEQUENOM platform technology.Primary-resected tumor tissue represents less than 3% of all diagnostic specimens in this disease, highlighting the limited access to tissue sufficient for comprehensive genomic analyses. We identified an activating M918T RET somatic mutation in a metastatic SCLC tumor specimen. Bioinformatic search identified RET mutations in other SCLC studies. Stable overexpression of both mutant M918T and wild-type RET in two SCLC cell lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased cell proliferation, particularly by mutant RET. Stable cells became sensitized to the RET tyrosine kinase inhibitors, vandetanib and ponatinib. Further analysis of RET mRNA expression in SCLC revealed wide variability in both cells and tumors, and SCLC cells demonstrated significantly higher RET expression compared with adenocarcinoma lung cells.Our data suggest that a subpopulation of SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET. Coupled with the presence of RET fusion proteins in non-small-cell lung cancer, our data indicate an emerging role for RET in SCLC.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|BRIP1||A745P||missense||unknown||BRIP1 A745P does not lie within any known functional domains of the Brip1 protein (UniProt.org). A745P has been identified in sequencing studies (PMID: 25122427), but has not been characterized and therefore, its effect on Brip1 protein function is unknown (PubMed, Feb 2022).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|RET M918T||lung small cell carcinoma||sensitive||Vandetanib||Preclinical||Actionable||In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427).||25122427|
|RET M918T||lung small cell carcinoma||sensitive||Ponatinib||Preclinical||Actionable||In a preclinical study, Iclusig (ponatinib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427).||25122427|
|RET wild-type||lung small cell carcinoma||sensitive||Ponatinib||Preclinical||Actionable||In a preclinical study, Iclusig (ponatinib) inhibited growth of small cell lung carcinoma lines expressing wild-type RET (PMID: 25122427).||25122427|
|RET wild-type||lung small cell carcinoma||sensitive||Vandetanib||Preclinical||Actionable||In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing wild-type RET (PMID: 25122427).||25122427|