Association of <i>EGFR</i> mutation or <i>ALK</i> rearrangement with expression of DNA repair and synthesis genes in never‐smoker women with pulmonary adenocarcinoma

Ren, Shengxiang; Chen, Xiaoxia; Kuang, Peng; Zheng, Li-Mou; Su, Chunxia; Li, Jia-Yu; Li, Bing; Yong-shen, Wang; Liu, Lu; Hu, Qiong; Zhang, Jie; Tang, Liang; Li, Xuefei; Zhou, Caicun; Schmid-Bindert, Gerald

doi:10.1002/cncr.27603

Cited by 51 publications

(28 citation statements)

References 38 publications

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“…In addition, only 10% of patients did not harbor any detected mutation in these genes. Ren et al reported EGFR mutation in 70% and ALK rearrangement in 9.6% in adenocarcinomas from never-smoker Chinese women (see Supplemental Table 5 for summary of these studies) [27]. The incidences of mutation detected in this study are consistent with those of previous studies.…”

Section: Discussionsupporting

confidence: 90%

Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

et al. 2015

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The aim of this study was to determine the distribution of known oncogenic driver mutations in female never-smoker Asian patients with lung adenocarcinoma. We analyzed 214 mutations across 26 lung cancer-associated genes and three fusion genes using the MassARRAY® LungCarta Panel and the ALK, ROS1, and RET fusion assays in 198 consecutively resected lung adenocarcinomas from never-smoker females at a single institution. EGFR mutation, which was the most frequent driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS, PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7%, 4%, 2.5%, 1.5%, 1%, 1%, and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never-smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas tended to have a lower frequency of known driver gene mutations than other histologic subtypes. EGFR mutation was associated with older age and a predominantly acinar pattern, while ALK rearrangement was associated with younger age and a predominantly solid pattern. Lung cancer in never-smoker Asian females is a distinct entity, with the majority of these cancers developing from oncogenic mutations.

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Section: Discussionsupporting

confidence: 90%

Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

et al. 2015

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“…Thus the obtained biomarker results are in concordance with previous reports and demonstrate that the used method is feasible for multiple biomarker testing in a routine setting. In line with our previous and Gandara’s report [20]–[21], the ERCC1 levels in the patients with EGFR mutation were significantly lower than the wild type, which indicated that EGFR mutation could also be helpful as a selection criterion for the optimal chemotherapy regimen.…”

Section: Discussionsupporting

confidence: 89%

EBUS-TBNA Provides Highest RNA Yield for Multiple Biomarker Testing from Routinely Obtained Small Biopsies in Non-Small Cell Lung Cancer Patients - A Comparative Study of Three Different Minimal Invasive Sampling Methods

et al. 2013

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BackgroundMultiple biomarker testing is necessary to facilitate individualized treatment of lung cancer patients. More than 80% of lung cancers are diagnosed based on very small tumor samples. Often there is not enough tissue for molecular analysis. We compared three minimal invasive sampling methods with respect to RNA quantity for molecular testing.Methods106 small biopsies were prospectively collected by three different methods forceps biopsy, endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA), and CT-guided core biopsy. Samples were split into two halves. One part was formalin fixed and paraffin embedded for standard pathological evaluation. The other part was put in RNAlater for immediate RNA/DNA extraction. If the pathologist confirmed the diagnosis of non-small cell lung cancer(NSCLC), the following molecular markers were tested: EGFR mutation, ERCC1, RRM1 and BRCA1.ResultsOverall, RNA-extraction was possible in 101 out of 106 patients (95.3%). We found 49% adenocarcinomas, 38% squamouscarcinomas, and 14% non-otherwise-specified(NOS). The highest RNA yield came from endobronchial ultrasound guided needle aspiration, which was significantly higher than bronchoscopy (37.74±41.09 vs. 13.74±15.53 ng respectively, P = 0.005) and numerically higher than CT-core biopsy (37.74±41.09 vs. 28.72±44.27 ng respectively, P = 0.244). EGFR mutation testing was feasible in 100% of evaluable patients and its incidence was 40.8%, 7.9% and 14.3% in adenocarcinomas, squamouscarcinomas and NSCLC NOS subgroup respectively. There was no difference in the feasibility of molecular testing between the three sampling methods with feasibility rates for ERCC1, RRM1 and BRCA1 of 91%, 87% and 81% respectively.ConclusionAll three methods can provide sufficient tumor material for multiple biomarkers testing from routinely obtained small biopsies in lung cancer patients. In our study EBUS guided needle aspiration provided the highest amount of tumor RNA compared to bronchoscopy or CT guided core biopsy. Thus EBUS should be considered as an acceptable option for tissue acquisition for molecular testing.

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“…Gandara et al investigated the association between ERFR mutation and ERCC1 mRNA levels in 1207 NSCLC tumor samples, and reported that tumors harboring activating EGFR mutations were more likely to express low levels of ERCC1 mRNA [17]. Re et al also reported that specimens harboring EGFR mutations were likely to have low expression of ERCC1 [21], and Lee et al, using immunohistochemistry, found a significant correlation between EGFR mutation and low levels of ERCC1 in tumor cells [22]. In agreement with these results, we found a significant correlation between ERCC1 expression and EGFR mutation (P = 0.030).…”

Section: Discussionmentioning

confidence: 99%

“…This method is able to detect 11 different mutations in the presence of a 100- to 1,000-fold wild-type EGFR background [16]. These 11 mutations account for 95% of all EGFR mutations found in Japanese patients, suggesting that the remaining 5% cannot be detected by the PNA-LNA PCR clamp method [21]. Therefore it is possible some patients in whom mutations were not detected may actually have harbored mutations.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of EGFR Mutation and ERCC1 in Patients with Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy

et al. 2013

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BackgroundIn order to improve the outcome of patients with non-small cell lung cancer (NSCLC), a biomarker that can predict the efficacy of chemotherapy is needed. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC.MethodsWe conducted a retrospective study to analyze the relationships between EGFR mutations or ERCC1 expression and progression-free survival (PFS) in patients with NSCLC who received platinum-based chemotherapy. EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and immunohistochemistry was used to examine the expression of ERCC1 in tumor samples obtained from the patients.ResultsAmong the NSCLC patients who received platinum-based chemotherapy, the median PFS was significantly better in those who had never smoked and those with exon 19 deletion, and the median overall survival (OS) was significantly better in those who had never smoked, those with exon 19 deletion, and women. Cox regression analysis revealed that exon 19 deletion and having never smoked were significantly associated with both PFS and OS. Subset analysis revealed a significant correlation between ERCC1 expression and EGFR mutation, and ERCC1-negative patients with exon 19 deletion had a longer PFS than the other patients; ERCC1-positive patients without exon 19 deletion had a shorter PFS than the other patients.ConclusionsOur results indicate that among NSCLC patients receiving platinum-based chemotherapy, those with exon 19 deletion have a longer PFS and OS. Our findings suggest that platinum-based chemotherapy is more effective against ERCC1-negative and exon 19-positive NSCLC.

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Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never‐smoker women with pulmonary adenocarcinoma

Cited by 51 publications

References 38 publications

Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

EBUS-TBNA Provides Highest RNA Yield for Multiple Biomarker Testing from Routinely Obtained Small Biopsies in Non-Small Cell Lung Cancer Patients - A Comparative Study of Three Different Minimal Invasive Sampling Methods

Prognostic Value of EGFR Mutation and ERCC1 in Patients with Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy

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