scholarly journals hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer

2019 ◽  
Vol Volume 12 ◽  
pp. 3065-3075 ◽  
Author(s):  
Nan Li ◽  
Guang-Wei Tian ◽  
Ling-Rong Tang ◽  
Guang Li
Keyword(s):  
Lung Cancer ◽  
Homologous Recombination ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Homologous Recombination Pathway ◽  
Recombination Pathway

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 Non–Small Cell Lung Cancer Exhibits Transcript Overexpression of Genes Associated with Homologous Recombination and DNA Replication Pathways

2009 ◽  
Vol 69 (8) ◽  
pp. 3390-3396 ◽  
Author(s):  
Silvia Saviozzi ◽  
Paolo Ceppi ◽  
Silvia Novello ◽  
Paolo Ghio ◽  
Marco Lo Iacono ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Replication ◽  
Homologous Recombination ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Homologous recombination and DNA repair mutations in patients treated with carboplatin and nab-paclitaxel for metastatic non-small cell lung cancer

Lung Cancer ◽  
2019 ◽  
Vol 134 ◽  
pp. 167-173 ◽  
Author(s):  
Dwight H. Owen ◽  
Terence M. Williams ◽  
Erin M. Bertino ◽  
Xiaokui Mo ◽  
Amy Webb ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair–targeted therapies

2021 ◽  
Vol 13 (578) ◽  
pp. eabc7488
Author(s):  
Camille Tlemsani ◽  
Nobuyuki Takahashi ◽  
Lorinc Pongor ◽  
Vinodh N. Rajapakse ◽  
Manoj Tyagi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Homologous Recombination ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Tobacco Exposure ◽  
Small Cell Lung ◽  
Inherited Susceptibility ◽  
Platinum Based Chemotherapy

Because tobacco is a potent carcinogen, secondary causes of lung cancer are often diminished in perceived importance. To assess the extent of inherited susceptibility to small cell lung cancer (SCLC), the most lethal type of lung cancer, we sequenced germline exomes of 87 patients (77 SCLC and 10 extrapulmonary small cell) and considered 607 genes, discovering 42 deleterious variants in 35 cancer-predisposition genes among 43.7% of patients. These findings were validated in an independent cohort of 79 patients with SCLC. Loss of heterozygosity was observed in 3 of 14 (21.4%) tumors. Identification of variants influenced medical management and family member testing in nine (10.3%) patients. Unselected patients with SCLC were more likely to carry germline RAD51 paralog D (RAD51D), checkpoint kinase 1 (CHEK1), breast cancer 2 (BRCA2), and mutY DNA glycosylase (MUTYH) pathogenic variants than healthy controls. Germline genotype was significantly associated with the likelihood of a first-degree relative with cancer or lung cancer (odds ratio: 1.82, P = 0.008; and 2.60, P = 0.028), and longer recurrence-free survival after platinum-based chemotherapy (P = 0.002), independent of known prognostic factors. Treatment of a patient with relapsed SCLC and germline pathogenic mutation of BRCA1 interacting protein C-terminal helicase 1 (BRIP1), a homologous recombination–related gene, using agents synthetically lethal with homologous recombination deficiency, resulted in a notable disease response. This work demonstrates that SCLC, currently thought to result almost exclusively from tobacco exposure, may have an inherited predisposition and lays the groundwork for targeted therapies based on the genes involved.

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