Gene fusions have a very important role in the study of cancer development. In this regard, predicting the probability of protein fusion transcripts of developing into a cancer is a very challenging and yet not fully explored research problem. To thi...
Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational...
A single primary cilium projects from most vertebrate cells to guide cell fate decisions. A growing list of signaling molecules is found to function through cilia and control ciliogenesis, including the fibroblast growth factor receptors (FGFR). Aber...
CD74 is a type II cell surface receptor found to be highly expressed in several hematological and solid cancers, due to its ability to activate pathways associated with tumor cell survival and proliferation. Over the past 16 years, CD74 has emerged a...
Non-small cell lung cancer (NSCLC) is operated commonly by diverse genetic alterations, and oncogenic fusions represent a significant therapeutic role. Common fusions include ALK, ROS1, RET, and NTRK, signaling pathways in tumorigenesis. Recent advan...
Constitutive activation of oncogenes by fusion to partner genes, caused by chromosome translocation and inversion, is a critical genetic event driving lung carcinogenesis. Fusions of the tyrosine kinase genes ALK (anaplastic lymphoma kinase), ROS1 (c...
Here, we investigated the detailed molecular oncogenic mechanisms of a novel receptor tyrosine kinase (RTK) fusion, KLC1-ROS1, with an adapter molecule, KLC1, and an RTK, ROS1, discovered in pediatric glioma, and we explored a novel therapeutic targe...
Chromosomal translocations creating fusion genes are common cancer drivers. The oncogenic ETV6-NTRK3 (EN) gene fusion joins the sterile alpha domain of the ETV6 transcription factor with the tyrosine kinase domain of the neurotrophin-3 receptor NTRK3...
In 2012, whole-transcriptome sequencing analysis led to the discovery of recurrent fusions involving the FGFR3 and TACC3 genes as the main oncological driver in a subset of human glioblastomas. Since then, FGFR3-TACC3 fusions have been identified in...
Drugs targeting receptor tyrosine kinase (RTK) oncogenic fusion proteins demonstrate impressive anti-cancer activities. The fusion presence in the cancer is the respective drug prescription biomarker, but their identification is challenging as both t...
Some pancreatic ductal-type (PDADK) and lung adenocarcinomas (LADK) lacking other molecular drivers are reported to harbor NRG1 fusions as potential novel therapeutic targets. We investigated the feasibility of a fluorescent in situ hybridization (FI...
Background: Gene fusions occur when two independent genes form a hybrid gene through genomic rearrangements, which often leads to abnormal expression and function of an encoded protein. In hematological and solid cancers, oncogenic fusions may be pro...
Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription fa...
Invasive melanoma is the deadliest type of skin cancer, with 101,110 expected cases to be diagnosed in 2021. Recurrent BRAF and NRAS mutations are well documented in melanoma. Biologic implications of gene fusions and the efficacy of therapeutically...
Accurate detection of oncogenic gene fusions is becoming increasingly important given the availability of highly effective targeted therapies. However, their identification in clinical practice remains challenging due to the rarity of individual even...
The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogeni...
Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and c...
Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein—FGFR3-TAC...
Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the e...
Background: In clinical practice, various methods are used to identify ALK gene rearrangements in tumor samples, ranging from “classic” techniques, such as IHC, FISH, and RT-qPCR, to more advanced highly multiplexed approaches, such as Na...
A heterogeneous genetic subtype of B-cell precursor acute lymphoblastic leukemia is driven by constitutive kinase-activation, including patients with JAK2 fusions. In our study, we model the impact of a novel JAK2 fusion protein on hematopoietic deve...
Chromosomal rearrangements are implicated in the pathogenesis of several human malignancies, but, concurrently, they also represent targetable opportunities, as exemplified by imatinib (Gleevec), which targets the BCR-ABL gene fusion in myeloid leuke...
The tropomyosin receptor kinases family (TrkA, TrkB, and TrkC) supports neuronal growth, survival, and differentiation during development, adult life, and aging. TrkA/B/C downregulation is a prominent hallmark of various neurological disorders includ...
The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (...
Fusion genes have been identified as oncogenes in several solid tumors including lung, colorectal, and stomach cancers. Here, we characterized the fusion gene, VAPA-Rab31, discovered from RNA-sequencing data of a patient with lung adenocarcinoma who...
Oncogenic fusion proteins, arising from chromosomal rearrangements, have emerged as prominent drivers of tumorigenesis and crucial therapeutic targets in cancer research. In recent years, the potential of small molecular inhibitors in selectively tar...
Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients...
We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (KIF5B)-NTRK1 gene fusion that responds well to entrectinib. Moreover, KIF5B-NTRK1 gene chimera has been shown to be an oncogene, activating both the MAPK a...
NUP98-NSD1-positive acute myeloid leukemia (AML) is a poor prognostic subgroup that is frequently diagnosed in pediatric cytogenetically normal AML. NUP98-NSD1-positive AML often carries additional mutations in genes including FLT3, NRAS, WT1, and MY...
NF-κB signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-κB activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of...
Nucleoporin 214 (NUP214) is a component of the nucleopore molecular complex, but in addition to this role in nucleocytoplasmic transport it is also involved in the regulation of gene transcription/translation, intracellular signaling, cell cycle prog...
It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and p...
High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10–12% of pediatric HGGs (pHGG) occur in children younger than five years of age at dia...
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers characterized by the excessive production of blood cells in the bone marrow. These disorders arise from acquired genetic driver mutations, with or without underlying genetic predis...
Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC w...
Synovial sarcoma (SyS) is a rare aggressive soft tissue sarcoma carrying the chromosomal translocation t(X;18), encoding the fusion transcript SS18::SSX. The fusion oncoprotein interacts with both BAF enhancer complexes and polycomb repressor complex...
Rhabdomyosarcoma (RMS) is a family of soft tissue cancers that are related to the skeletal muscle lineage and predominantly occur in children and young adults. A specific chromosomal translocation t(2;13)(q35;q14) that gives rise to the chimeric onco...
Following the identification of the BCR-ABL1 (Breakpoint Cluster Region-ABelson murine Leukemia) fusion in chronic myelogenous leukemia, gene fusions generating chimeric oncoproteins have been recognized as common genomic structural variations in hum...
NUP98 fusions constitute a small subgroup of AML patients and remain a high-risk AML subtype. There are approximately 30 types of NUP98 fusions identified in AML patients. These patients show resistance to currently available therapies and poor clini...
We explored the rationale for treating glioblastoma (GBM) with regorafenib. In 103 newly diagnosed GBM patients, we assessed mutations, copy number variants (CNVs), fusions, and overexpression in 46 genes encoding protein kinases (PKs) potentially ta...
One common genetic alteration in cancer is gene fusion resulting from chromosomal translocations. The mechanisms that create such oncogenic fusion genes are not well understood. Previously, we provided the direct evidence that expression of a designe...
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase involved in neuronal and gut development. Initially discovered in T cell lymphoma, ALK is frequently affected in diverse cancers by oncogenic translocations. These translocations involve different...
Oncogenic Yes-associated protein (YAP) 1 fusions have been recently identified in several cases of meningioma mostly involving pediatric patients. The meningiomas harboring YAP1-MAML2, which is the most frequent fusion subtype, exhibit activated YAP1...
Background: Oncogenic fusions of MAML2 with CRTC1, CRTC3, YAP1, and NR1D1 retain the MAML2 transactivating domain (TAD) and are believed to drive aberrant gene transcription. While the oncogenic roles of these known fusions have been established, we...
In principle, an oncogene is a cellular gene (proto-oncogene) that is dysfunctional, due to mutation and fusion with another gene or overexpression. Generally, oncogenes are viewed as deregulating cell proliferation or suppressing apoptosis in drivin...
Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up...
The management of non-small cell lung cancer (NSCLC) has transformed with the discovery of therapeutically tractable oncogenic drivers. In addition to activating driver mutations, gene fusions or rearrangements form a unique sub-class, with anaplasti...
(1) Background: The main objectives of our study are (i) to determine the prevalence of NTRK (neurotrophic tyrosine kinase) fusions in a routine diagnostic setting in NSCLC (non-small cell lung cancer) and (ii) to investigate the feasibility of scree...
The detection of ALK receptor tyrosine kinase (ALK), ROS proto-oncogen1, receptor tyrosine kinase (ROS1), ret proto-oncogen (RET), and MET proto-oncogen exon 14 skipping (METΔex14) allows for the selection of specific kinase inhibitor treatment...
Oncogenic gene fusions are hybrid genes that result from structural DNA rearrangements, leading to unregulated cell proliferation by different mechanisms in a wide variety of cancer. This has led to the development of directed therapies to antagonize...
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