scholarly journals Genomic based analyses reveal unique mutational profiling and identify prognostic biomarker for overall survival in Chinese small-cell lung cancer

2019 ◽  
Vol 49 (12) ◽  
pp. 1143-1150 ◽  
Author(s):  
Yu Wang ◽  
Xiao Han ◽  
Xingwen Wang ◽  
Wei Sheng ◽  
Zheng Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Mutations ◽  
Small Cell ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Mutational Profiling ◽  
Mutation Burden ◽  
Clonal Mutation

Abstract Objective As an aggressive subtype of lung cancer, small-cell lung cancer (SCLC) presents a poor prognosis. Although molecular and clinical characteristics have been established for SCLC, limited investigation has been performed for predicting survival of SCLC patients. Methods Genomic alterations were profiled in Chinese SCLC patients (N = 37) using targeted sequencing. Clonal mutation burden (CMB) integrated the number of mutations with the clonal structure of the tumor. Specific pathways involving DNA damage repair (DDR) and cell cycle as well as CMB were studied as potential biomarkers for prognosis of SCLC. Results TP53 and RB1 gene mutations were the most common alterations (91.9% and 83.8%, respectively), followed by LRP1B, FAM135B, SPTA1, KMT2D, FAT1, and NOTCH3. Survival analysis revealed that mutation status of the DDR pathway was associated with worse OS in our cohort. Importantly, patients with higher CMB exhibited worse OS in our cohort and this observation was successfully validated in the cBioportal cohort. Moreover, multivariate analysis demonstrated CMB as a promising independent prognostic factor for OS in Chinese SCLC patients. Interestingly, patients with loss of function of RB1, validated by immunohistochemistry staining, appeared to have worse OS. Conclusions The mutational profiling of Chinese SCLC patients signified an ethnicity dependent component. CMB was firstly found to be associated with OS of Chinese SCLC patients and could be regarded as a prognostic marker for SCLC.

Comparison of molecular signatures in small cell lung cancer with or without homologous recombination associated gene mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20580-e20580
Author(s):  
Lili Fu ◽  
Feifei Li ◽  
Dandan Ren ◽  
Beibei Mao ◽  
Huan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Homologous Recombination ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Gene Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Homologous Recombination Deficiency

e20580 Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. Recently, Immune checkpoint inhibitors (ICIs) have been shown to have the potential to improve the prognosis of SCLC, but little is known about immunotherapeutic biomarkers. Homologous recombination deficiency (HRD) is demonstrated to be a response predictor to immunotherapies in gynecologic cancers, while limited studies were reported in small cell lung cancer. Herein, we analyze the mutational pattern of HRR related genes in a Chinese SCLC cohort and further analyze the relationship between HRR-gene mutations and tumor mutational burden. Methods: Target gene sequencing (543 genes) was performed in 133 Genecast cohort with small cell lung cancer. PD-L1 expression were evaluated for 90 among 133 patients using the SP142 PD-L1 immunohistochemistry assay. Results: Among 133 patients, 47 (35.3%) had HRR-gene mutations. ATM (8.3%), NBN (4.5%) and BRCA2 (4.5%) were the top 3 mutated HRR-gene in the cohort，followed by ATR (3.8%), BARD1 (3.8%), BRCA1 (3.8%), PALB2 (3.8%), RAD50 (3.8%), CHEK2 (3.0%), BLM (3.0%), BRIP1(2.3%), CHEK1(1.5%), RAD52(1.5%), and MRE11A (0.8%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (11/47, 23.4%) and 3 (3/47, 6.4%) patients, respectively. 1 (1/47, 2.1%) patient carried both germline and somatic variants. Genomic landscape revealed that TP53 and RB1 were commonly mutated genes in SCLC cohort. Mutations in KMT2D, AR and RTK-RAS pathway occurred more frequently in the HRR-Mut group, compared with the wildtype ones. Furthermore, we found that mutations in HRR-gene were associated with high TMB (Wilcoxon, p = 0.048), and patients with high TMB (≥median) showed a higher proportion of positive PD-L1 expression in 90 SCLC patients. Conclusions: Our data indicated that genomic alterations associated with HRR-genes have a positive correlation with high TMB, and detection of HRR-gene mutation status probably could help identify patients who might benefit from immune checkpoint blockade therapy. Keywords: Small cell lung cancer, Homologous recombination deficiency, Immunotherapy.

scholarly journals Detection of EGFR gene mutations in non-small cell lung cancer: Lessons from a single-institution routine analysis of 1,403 tumor samples

2013 ◽  
Vol 43 (4) ◽  
pp. 1045-1051 ◽  
Author(s):  
AUDREY VALLEE ◽  
CHRISTINE SAGAN ◽  
ANNE-GAELLE LE LOUPP ◽  
KALYANE BACH ◽  
THOMAS DEJOIE ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Mutations ◽  
Small Cell ◽  
Routine Analysis ◽  
Small Cell Lung ◽  
Single Institution ◽  
Egfr Gene

Abstract 258: Characterizing cancer gene mutations in non-small cell lung cancer from African American patients

2014 ◽  
Author(s):  
Aliccia Bollig-Fischer ◽  
Shirish Gadgeel ◽  
Wei Chen ◽  
Michele Cote ◽  
Ann G. Schwartz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
African American ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Mutations ◽  
Small Cell ◽  
Cancer Gene ◽  
Small Cell Lung

scholarly journals Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 690 ◽  
Author(s):  
Arik Bernard Schulze ◽  
Georg Evers ◽  
Andrea Kerkhoff ◽  
Michael Mohr ◽  
Christoph Schliemann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Molecular Pathways ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Therapeutic Concept ◽  
Platinum Based Chemotherapy

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.

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