The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.
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http://dx.doi.org/10.1016/j.mrfmmm.2004.09.011 | DOI Listing |
Nat Commun
January 2024
Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors.
View Article and Find Full Text PDFMol Cancer Ther
January 2024
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non-small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments.
View Article and Find Full Text PDFBMC Cancer
April 2023
1 DNA Way, Genentech, Inc, South San Francisco, CA, 94080, USA.
Background: KRAS mutations occur frequently in advanced non-small cell lung cancer (aNSCLC); the G12C mutation is the most prevalent. Alterations in STK11 or KEAP1 commonly co-occur with KRAS mutations in aNSCLC. Using real-world data, we assessed the effect of KRAS G12C mutation with or without STK11 and/or KEAP1 mutations on overall survival (OS) in patients with aNSCLC receiving cancer immunotherapy (CIT), chemotherapy, or both in first line (1L) and second line (2L).
View Article and Find Full Text PDFHeliyon
July 2022
Area of Bioscience and Biotechnology, School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi City, Ishikawa, 923-1292, Japan.
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is genetically altered in several cancers, including NSCLC, melanoma, lymphoma, and other tumors. Although is associated with various cancers, the relationship between expression and patient prognosis in different cancers is poorly understood. Here, using multidimensional approaches, we revealed the correlation between expression and the clinical outcomes of patients with LUAD, melanoma, OV, DLBC, AML, and BC.
View Article and Find Full Text PDFCancers (Basel)
June 2022
Bowel Cancer and Biomarker Laboratory, Kolling Institute, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Early T stage colorectal cancers (CRC) that invade lymph nodes (Stage IIIA) are rare and greatly under-represented in large-scale genomic mapping projects. We retrieved 10 Stage IIIA CRC cases, matched these to 16 Stage 1 CRC cases (T1 depth without lymph node metastasis) and carried out deep sequencing of 409 genes using the IonTorrent system. Tumour mutational burdens (TMB) ranged from 2.
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