Expression and copy number gains of the <i>RET</i> gene in 631 early and mid stage non‐small cell lung cancer cases

Tan, Ling; Hu, Yerong; Tao, Yongguang; Wang, Bin; Xiao, Jun; Tang, Zhihua; Lu, Ting; Tang, Hao

doi:10.1111/1759-7714.12603

Cited by 13 publications

(7 citation statements)

References 33 publications

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“…Although RET rearrangements are infrequent, screening as part of a multigene panel or in patients where other lung cancer genes have been excluded, is recommended to identify patients who may benefit from RET targeted therapies (below) (Kalemkerian et al, 2018). Interestingly, recent studies indicate that increased expression of wildtype RET occurs in an even larger pool of NSCLC, where it may be linked to poor tumor differentiation (Tan et al, 2018), suggesting that, in addition to RET fusions, GFL-RET signaling may also contribute to these tumors.…”

Section: Ret Dependent Gfl Independent Cancersmentioning

confidence: 99%

GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential

Mulligan

2019

Front. Physiol.

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The Glial cell line-derived neurotrophic Family Ligands (GFL) are soluble neurotrophic factors that are required for development of multiple human tissues, but which are also important contributors to human cancers. GFL signaling occurs through the transmembrane RET receptor tyrosine kinase, a well-characterized oncogene. GFL-independent RET activation, through rearrangement or point mutations occurs in thyroid and lung cancers. However, GFL-mediated activation of wildtype RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET and GFL expression have been implicated in metastasis or invasion in diverse human cancers including breast, pancreatic, and prostate tumors, where they are linked to poorer patient prognosis. In addition to directly inducing tumor growth in these diseases, GFL-RET signaling promotes changes in the tumor microenvironment that alter the surrounding stroma and cellular composition to enhance tumor invasion and metastasis. As such, GFL RET signaling is an important target for novel therapeutic approaches to limit tumor growth and spread and improve disease outcomes.

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Section: Ret Dependent Gfl Independent Cancersmentioning

confidence: 99%

GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential

Mulligan

2019

Front. Physiol.

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“…Collectively, our data demonstrate significant intra-tumoral heterogeneity in PACC. Furthermore, classic NSCLC driver mutations [29][30][31][32][33] do not drive tumor development in this subset of lung carcinoma.…”

Section: Clonal Diversitymentioning

confidence: 99%

Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma

Zhao

Liu

et al. 2018

Cancer Biology & Therapy

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Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.

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“…Lung cancer is a well-known malignant disease, with the highest morbidity and mortality worldwide, moreover, nearly 40% patients were found with metastatic lesions at diagnosis [ 1 , 2 ]. Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of total lung cancer pathological types, and it mainly consists of adenocarcinoma and squamous cell carcinoma [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer

Zhou

Duan

et al. 2018

Bioscience Reports

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Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P<0.001) and mRNA levels (P<0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P<0.001), and chemotherapy (P<0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P<0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.

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Expression and copy number gains of the RET gene in 631 early and mid stage non‐small cell lung cancer cases

Cited by 13 publications

References 33 publications

GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential

GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential

Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma

Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer

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