New Targetable Oncogenes in Non–Small-Cell Lung Cancer

Oxnard, Geoffrey R.; Binder, Adam; Jänne, Pasi A.

doi:10.1200/jco.2012.42.9829

Cited by 271 publications

(211 citation statements)

References 76 publications

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“…The EML4-ALK fusion gene is found in 3%-5% of NSCLCs, and is detected by the U.S. Food and Drug Administration (FDA)-approved companion diagnostic breakapart fluorescence in situ hybridization (FISH) assay from Vysis (Abbott Laboratories, Abbott Park, IL, https://www. abbottmolecular.com), as well as a more recently approved immunohistochemistry (IHC) assay [2,3]. EML4-ALK fusions in NSCLC occur in at least 8 variants, with all known variants having a breakpoint in intron 19 of ALK, but with a variety of introns in EML4 experiencing rearrangement, resulting in inclusion of differing fragments of the N-terminal region of EML4 [4].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization

Ali¹,

Hensing

Schrock³

et al. 2016

The Oncologist

111

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Introduction. For patients with non-small cell lung cancer (NSCLC) tobenefitfromALKinhibitors,sensitiveandspecificdetectionofALK genomic rearrangements is needed. ALK break-apart fluorescence in situ hybridization (FISH) is the U.S. Food and Drug Administration approved and standard-of-care diagnostic assay, but identification of ALK rearrangements by other methods reported in NSCLC cases that tested negative for ALK rearrangements by FISH suggests a significant false-negative rate. We report here a large series of NSCLC cases assayed by hybrid-capture-based comprehensive genomic profiling (CGP) in the course of clinical care. Materials and Methods. Hybrid-capture-based CGP using nextgenerationsequencingwasperformedinthe course ofclinicalcare of 1,070 patients with advanced lung cancer. Each tumor sample was evaluated for all classes of genomic alterations, including base-pair substitutions, insertions/deletions, copy number alterations and rearrangements, as well as fusions/rearrangements.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization

Ali¹,

Hensing

Schrock³

et al. 2016

The Oncologist

111

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“…Lung cancer is one of the most common cancer types all over the world, and a number of previous studies have identified a large quantity of lung cancer driver genes, such as EGFR, Her2, AKT1, NRAS, PIK3CA, BRAF, ALK-fusion and RET-fusion (5)(6)(7)(8). Somatic mutations of these genes have been recurrently identified in lung cancer samples (5)(6)(7)(8). However, unlike in sporadic lung cancer, the molecular mechanisms behind inherited lung cancer remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…For example, epidermal growth factor receptor (EGFR) mutations (6), EML4/ALK fusion genes (7), RAS mutations, BRAF mutations and PI3K/mTOR mutations are frequently observed in lung cancer tissues, and are predictive of response to targeted therapies (8).…”

Section: Introductionmentioning

confidence: 99%

Sequencing study on familial lung squamous cancer

Wang

et al. 2015

Oncology Letters

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Abstract. Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer-related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer.

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“…It was suggested that amplification or overexpression of this gene has been shown to play an important role in the pathogenesis and progression of certain types of cancer (17,25,26). In breast cancer, ErbB2 was found to upregulate b-catenin via inactivation of GSK-3b by the Erk pathway (13).…”

Section: Discussionmentioning

confidence: 99%

Survival and Inflammation Promotion Effect of PTPRO in Fulminant Hepatitis Is Associated with NF-κB Activation

Jiang

Chen

Hou

et al. 2014

The Journal of Immunology

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Previous investigations demonstrated that protein tyrosine phosphatase, receptor type, O (PTPRO) acts as a tumor suppressor in liver cancer; however, little is known about its role in liver inflammation. Thus, we investigated the role of PTPRO in fulminant hepatitis (FH) using a Con A–induced mouse model. Significantly more severe liver damage, but attenuated inflammation, was detected in PTPRO-knockout (KO) mice, and PTPRO deficiency could confer this phenotype to wild-type mice in bone marrow transplantation. Moreover, hepatocytes with PTPRO depletion were more sensitive to TNF-α–induced apoptosis, and secretion of cytokines was significantly decreased in both T and NK/NKT cells and led to marked impairment of NF-κB activation. Intriguingly, wild-type and PTPRO-KO cells responded equally to TNF-α in activation of IKK, but NF-κB activation was clearly decreased in PTPRO-KO cells. PTPRO associated with ErbB2, and loss of PTPRO potentiated activation of the ErbB2/Akt/GSK-3β/β-catenin cascade. Increased β-catenin formed a complex with NF-κB and attenuated its nuclear translocation and activation. Importantly, in humans, PTPRO was much decreased in FH, and this was associated with enhanced β-catenin accumulation but reduced IFN-γ secretion. Taken together, our study identified a novel PTPRO/ErbB2/Akt/GSK-3β/β-catenin/NF-κB axis in FH, which suggests that PTPRO may have therapeutic potential in this liver disease.

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New Targetable Oncogenes in Non–Small-Cell Lung Cancer

Cited by 271 publications

References 76 publications

Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization

Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization

Sequencing study on familial lung squamous cancer

Survival and Inflammation Promotion Effect of PTPRO in Fulminant Hepatitis Is Associated with NF-κB Activation

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