Using Whole Genome Amplification (WGA) of Low-Volume Biopsies to Assess the Prognostic Role of EGFR, KRAS, p53, and CMET Mutations in Advanced-Stage Non-small Cell Lung Cancer (NSCLC)

Lim, Elaine; Zhang, Shen Li; Li, Jialiang; Yap, Wee See; Howe, Tse Chiang; Tan, Bien Peng; Lee, Yong Shyan; Wong, Daniel; Khoo, Kong Soo; Seto, Kar Yin; Tan, Lenny; Agasthian, Thirugnanam; Koong, Heng Nung; Tam, John Kit Chung; Tan, C. B.; Caleb, Michael George; Chang, Alex; Ng, Alan; Tan, Patrick

doi:10.1097/jto.0b013e3181913e28

Cited by 72 publications

(42 citation statements)

References 41 publications

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“…One of these studies found an association of TP53 mutations with shorter median OS in 70 cases of advanced NSCLC (4 vs. 9 months; ref. 41), whereas the other reported no association in a population of 88 patients (42). Taken together, all these discordant reports highlight the importance of establishing a widely accepted, clinically relevant classification of TP53 mutations that can allow the comparison of different studies.…”

Section: Discussionmentioning

confidence: 71%

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

134

149

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Purpose: TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.Experimental Design: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.Results: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P ¼ 0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P ¼ 0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P ¼ 0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.Conclusions: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.

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Section: Discussionmentioning

confidence: 71%

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

134

149

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“…30,67,69 Mutant K-ras was associated with poor overall survival of lung cancer patients. 35 The percentage of K-ras mutations present in lung adenocarcinomas from smokers is markedly higher than reported for non-smokers with lung adenocarcinoma (10-43 vs 0-8%), unlike EGFR tyrosine kinase domain mutations primarily occurring in lung adenocarcinomas of non-smokers. 25,69,[72][73][74][75][76] Most K-ras mutations in lung adenocarcinomas from smokers are characteristic G to T transversions, a typical mutation type induced by benzo(a)pyrene diolepoxide in vitro.…”

Section: K-ras Mutationmentioning

confidence: 62%

“…Kosaka et al 34 found that p53 mutations were not an independent prognostic factor in their cohort of patients with lung adenocarcinoma. Similarly, Lim et al 35 also reported that p53 mutations did not have a survival effect in 88 lung cancer patients with squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The controversy is probably due to the different methods or antibodies used to detect p53 gene mutation or protein expression, or the variation in stage classification of lung cancer patients.…”

Section: P53 Mutationmentioning

confidence: 99%

Genetic and epigenetic changes in lung carcinoma and their clinical implications

Wen

Zhang

et al. 2011

Modern Pathology

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Lung cancer is the leading cause of cancer deaths worldwide. Recent advance in targeted therapy for lung cancer patients with epidermal growth factor receptor (EGFR) mutations has demonstrated a promising development toward personalized therapy for lung cancer patients. The development of lung cancer is a complex process, involving a series of genetic and epigenetic changes. Tobacco smoke is the predominant etiologic risk factor for lung cancer. However, some lung cancers, especially adenocarcinomas, arise in patients who have never smoked, suggesting the importance of host genetic/epigenetic susceptibility in the occurrence and development of lung cancer. Understanding of these genetic and epigenetic changes will further aid in the biomarker-driven personalized therapy for lung cancer patients. In this review, we summarize the genetic and epigenetic alterations observed in lung cancers, including chromosomal loss of heterozygosity, tumor-suppressor gene mutation, gene methylation, histone modification, and microRNA expression changes. Clinical and preclinical studies have implied specific genetic/epigenetic changes for clinical application in lung cancer patients. However, more efforts are required in validation of the identified molecular markers in lung cancer patients for early detections, assessment for treatment response, and survival predictions.

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“…Hence, among a variety of potentially relevant molecules, ERCC1 and MAP-Tau were selected because they are involved in the process of 'recovery' from the platinum and taxane cytotoxic eVect, respectively [28][29][30]. Moreover, the expression of tyrosine kinase receptors (TKRs), such as HER2, EGFR and MET, has being thoroughly investigated [31][32][33] in solid tumors, but Wndings in gastric cancer are still controversial. Also, the role of the PTEN protein in gastric cancer is still unknown, whereas loss of heterozygosity of the relevant gene is found in many solid tumors.…”

mentioning

confidence: 99%

A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

Bamias

Karina

Papakostas

et al. 2010

Cancer Chemother Pharmacol

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Using Whole Genome Amplification (WGA) of Low-Volume Biopsies to Assess the Prognostic Role of EGFR, KRAS, p53, and CMET Mutations in Advanced-Stage Non-small Cell Lung Cancer (NSCLC)

Cited by 72 publications

References 41 publications

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Genetic and epigenetic changes in lung carcinoma and their clinical implications

A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

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