Comparison of small biopsy specimens and surgical specimens for the detection of EGFR mutations and EML4-ALK in non-small-cell lung cancer

Xiao, De Sheng; Lü, Can; Zhu, Wei; He, Qiu; Li, Yong; Fu, Chun Yan; Zhou, Jian; Liu, Shuang; Tao, Yong

doi:10.18632/oncotarget.10011

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…The echinoderm microtubule-associated protein-like (EML) 4–ALK-positive rate depends on tissue size and is higher in surgical as compared to small biopsy specimens [ 8 ]. In our study, the prevalence of ALK rearrangement in patients with Sq-LC was 1.36%; although all of the cases were diagnosed using small biopsy specimens, this rate was consistent with previous reports [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

et al. 2018

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Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.

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Section: Discussionmentioning

confidence: 99%

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

et al. 2018

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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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“…Previous studies have demonstrated that EGFR , a well-known oncogenic driver, contributes to the initiation and progression of lung cancer [ 23 , 24 , 25 ]. A subset of this investigation aimed to confirm whether there is a direct association between SNCA and the EGFR signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

SNCA Is a Functionally Low-Expressed Gene in Lung Adenocarcinoma

Yan

et al. 2018

Genes

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There is increasing evidence for the contribution of synuclein alpha (SNCA) to the etiology of neurological disorders, such as Parkinson’s disease (PD). However, little is known about the detailed role of SNCA in human cancers, especially lung cancers. Here, we evaluated the effects of SNCA on the occurrence and prognosis of lung adenocarcinoma (ADC). Comprehensive bioinformatics analyses of data obtained from the Oncomine platform, the human protein atlas (HPA) project and the cancer cell line encyclopedia (CCLE) demonstrated that SNCA expression was significantly reduced in both ADC tissues and cancer cells. The results of relevant clinical studies indicated that down-regulation of SNCA was statistically correlated with shorter overall survival time and post-progression survival time. Through analysis of datasets obtained from the Gene Expression Omnibus database, significant low levels of SNCA were identified in cisplatin-resistant ADC cells. Moreover, small interfering RNA (siRNA)-mediated knockdown of protein tyrosine kinase 7 (PTK7) elevated the expression of SNCA in the ADC cell lines H1299 and H2009. Our work demonstrates that low levels of SNCA are specifically found in ADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determination of the role of SNCA in ADC biology would give us some insightful information for further investigations.

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Comparison of small biopsy specimens and surgical specimens for the detection of EGFR mutations and EML4-ALK in non-small-cell lung cancer

Cited by 12 publications

References 32 publications

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma

SNCA Is a Functionally Low-Expressed Gene in Lung Adenocarcinoma

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