Unraveling the genomic complexity of small cell lung cancer

Karachaliou, Niki; Sosa, Aaron E.; Rosell, Rafael

doi:10.21037/tlcr.2016.07.02

Cited by 57 publications

(57 citation statements)

References 23 publications

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“…The percentages of TP53 mutations were comparable in patients with adenocarcinoma (48.3%) and small cell lung cancer (48.4%) (data not shown). All patients investigated in the present study with small cell lung cancer carried TP53 mutations, in line with previous studies (42), suggesting that a significant percentage of patients with small cell lung cancer have TP53 mutations. Next, the mutation spectra of patients with TP53 mutations were compared with patients without TP53 mutation (Fig.…”

Section: Resultssupporting

confidence: 93%

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Liu

Wang

et al. 2019

Oncol Lett

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Currently, in clinical settings, all TP53 mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for TP53 mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of TP53 mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture-based ultra-deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor-naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all TP53 mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different TP53 mutation classification systems in a large cohort of patients with advanced lung cancer.

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Section: Resultssupporting

confidence: 93%

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Liu

Wang

et al. 2019

Oncol Lett

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“…The data we present in terms of mutation prevalence resembles previously published cohorts. Unfortunately, the vast majority of patients analyzed in previous studies were smokers (31). RB1 is the most relevant mutational difference between smoker and non-smoker SCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

et al. 2019

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Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers ( n = 10) and never/ever-smokers ( n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases ( p = 0.04) and were older ( p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers ( p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET , and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

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“…A pooled analysis of randomized SCLC chemotherapy trials showed that female patients survived modestly longer than male patients [21]. Another study indicated that female sex is useful as a predictor for better long-term survival [22].…”

Section: Discussionmentioning

confidence: 99%

Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer

Chen

Qiao

et al. 2020

Journal of Oncology

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Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P = 0.004 ), mutant TP53 (PFS = 5.0 months, P = 0.011 ), and mutant BRCA2 (PFS = 6.7 months, P = 0.046 ) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038–6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096–3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721–12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181–0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.

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Unraveling the genomic complexity of small cell lung cancer

Cited by 57 publications

References 23 publications

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer

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