Coexistence of a Novel PRKCB-ALK, EML4-ALK Double-Fusion in a Lung Adenocarcinoma Patient and Response to Crizotinib

Luo, Jing; Gu, Dejian; Lu, Huasong; Liu, Si; Kong, Jinliang

doi:10.1016/j.jtho.2019.07.021

Cited by 21 publications

(16 citation statements)

References 4 publications

(5 reference statements)

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“…A few cases of co-existence of canonical and non-canonical ALK fusions has been reported in recent studies (29,30); however, its clinical relevance was largely unknown. We found that there were little differences in PFS after crizotinib treatment among different ALK fusion groups, whereas patients with complex ALK fusions had better OS.…”

Section: Discussionmentioning

confidence: 99%

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

et al. 2020

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BackgroundEchinoderm microtubule-associated protein-like 4 (EML4) is the canonical anaplastic lymphoma kinase (ALK) fusion partner in non-small cell lung cancer (NSCLC), and ALK-positive patients showed promising responses to ALK tyrosine kinase inhibitors (TKIs). However, studies that comprehensively investigate ALK TKI treatment in patients with different ALK fusion patterns are still lacking.MethodsNinety-eight ALK-positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling (CGP) was conducted to divide patients into different groups based on their ALK fusion patterns. Non-canonical ALK fusions were validated using RNA-sequencing.Results54.1% of patients had pure canonical EML4-ALK fusions, 19.4% carried only non-canonical ALK fusions, and 26.5% harbored complex ALK fusions with coexisting canonical and non-canonical ALK fusions. The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex ALK fusion group. Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010). The complex ALK fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies. Most identified non-canonical ALK fusions were likely to be expressed in tumors, and some of them formed canonical EML4-ALK transcripts during mRNA maturation.ConclusionOur results suggest NSCLC patients with complex ALK fusions could potentially have better treatment outcomes to ALK TKIs therapy. Also, diagnosis using CGP is of great value to identify novel ALK fusions and predict prognosis.

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Section: Discussionmentioning

confidence: 99%

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

et al. 2020

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“…Curation of PKC gene fusions 5' and 3' PKC fusions organized in Table S1, Table S2, and graphed in Figure 1, B and C were curated from the literature (18,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) and the following online databases: the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (mitelmandatabase.isb-cgc.org), the TCGA Tumor Fusion Gene Data Portal, ChimerDB v3.0, and COSMIC (cancer.sanger.ac.uk) (30,(38)(39)(40). Fusions were detected in the following cancer types: BFH, bladder urothelial carcinoma, BRCA, cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, clear cell renal cell carcinoma, kidney renal papillary cell carcinoma, acute myeloid leukemia, LGG, liver hepatocellular carcinoma, LUAD, LUSC, medulloblastoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, PGNT, prostate adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, T-cell acute lymphoblastic leukemia, and UCEC.…”

Section: Methodsmentioning

confidence: 99%

“…In order to assess the landscape of PKC fusions in cancer, we queried the literature and several online databases to curate a comprehensive list of all PKC gene fusions identified from patient tumor samples (Table S1) (18,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). The online databases utilized in this study include the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, the TCGA Tumor Fusion Gene Data Portal, ChimerDB v3.0, and the Catalogue of Somatic Mutations in Cancer (COSMIC) (30,(38)(39)(40).…”

Section: A Multitude Of Pkc Fusions Have Been Identified In Cancermentioning

confidence: 99%

Protein kinase C fusion proteins are paradoxically loss of function in cancer

Van

Kunkel

Baffi

et al. 2021

Journal of Biological Chemistry

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“…We retrospectively analyzed genomic profiling data of 1,312 patients with rare tumors from Geneplus database. This database contained patients enrolled from multiple hospitals of China from September 2015 to October 2019 (18,19). All patients received next-generation sequencing (NGS) testing in Geneplus-Beijing Institute after obtaining written informed consent.…”

Section: Patient Recruitmentmentioning

confidence: 99%

Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies

Wang

Chen²,

Tang

et al. 2020

Front. Oncol.

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Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcomes for patients with rare tumors. This study aims to discover opportunities for use of targeted therapies already approved for routine use in patients with rare tumors. Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiological data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal were compared with that of the Chinese population for targetable genomic alterations (TGAs). TGAs were defined as mutations of ALK,

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Coexistence of a Novel PRKCB-ALK, EML4-ALK Double-Fusion in a Lung Adenocarcinoma Patient and Response to Crizotinib

Abstract: ND, not detected; c.HGVS, description of coding DNA (c.) varients by human genome variation society (HGVS); p.HGVS, description of protein (p.) varients by HGVS. *describe a stop codon.

Cited by 21 publications

References 4 publications

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

Protein kinase C fusion proteins are paradoxically loss of function in cancer

Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies

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