Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory myofibroblastic tumors (IMT) are mesenchymal solid tumors that occur preferentially in children and young adults. They present as myofibroblastic cell proliferations accompanied by plasmocytes and lymphocytes. Recent cytogenetic and molecular observations showed non-random abnormalities of chromosomal band 2p23 resulting in a rearrangement of the ALK gene. This finding of a specific gene alteration suggests a neoplastic rather than a reactive inflammatory process for IMT tumorigenesis. ALK is a tyrosine kinase oncogene initially found to be rearranged in anaplastic large-cell lymphomas (ALCL). Of note, the breakpoints within ALK, and also within some of the ALK fusion gene partners, such as TPM3 or CLTC, are similar in IMT and ALCL. The consistent involvement of ALK, together with the diversity of partner genes, underlines the central role of ALK constitutive activation in IMT development, as well as the importance of homodimerization mechanisms of the chimeric fusion proteins in this activation. Immunohistochemical analyses performed on paraffin embedded tissue sections have shown positive ALK expression with cytoplasmic localization in half of the IMT cases containing the molecular ALK rearrangement. In conclusion, these novel molecular data have defined a group of IMT of neoplastic origin characterized by the presence of ALK alterations. The description of ALK gene rearrangements in IMT and ALCL is the second example, after the observation of ETV6-NTRK3 in congenital fibrosarcoma and in a case of chronic myeloid leukemia, of identical gene fusions occurring in two different cell lines: hematopoietic and mesenchymal. The search for rearrangement of ALK by fluorescence in situ hybridization (FISH) is a useful complementary tool for IMT diagnosis.
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PMID:[Inflammatory myofibroblastic tumors]. 1259 87

Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a "breakpoint analysis" pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis.
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PMID:Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types. 2363 31