The mutation rates of EGFR in non-small cell lung cancer and KRAS in colorectal cancer of Chinese patients as detected by pyrosequencing using a novel dispensation order
Autor: | Guohua Xie, Ping-ping Wu, Yunchuan Xu, Fang Xie, Ming-Ming Yang, Li Li, Xiangliang Yuan, Ling Xu, Yanhui Ma, Lisong Shen |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Oncology
Adult Male Cancer Research Mutation rate medicine.medical_specialty Lung Neoplasms Colorectal cancer EGFR Biology medicine.disease_cause NSCLC Exon Asian People Mutation Rate Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma KRAS Humans Allele Lung cancer neoplasms Aged Aged 80 and over Pyrosequencing Sequence Analysis DNA Middle Aged medicine.disease digestive system diseases respiratory tract diseases CRC ErbB Receptors Cancer research ras Proteins Adenocarcinoma Female FFPE sample Research Article |
Zdroj: | Journal of Experimental & Clinical Cancer Research : CR |
ISSN: | 1756-9966 0392-9078 |
Popis: | Background The purpose of this study was to develop a cost-effective approach for the determination of EGFR and KRAS mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) samples from Chinese patients based on a sensitive pyrosequencing (PS) technique. Methods The NSCLC and CRC cell lines were tested to determine the limitation of detection and reproducibility of the PS method. In addition, 494 NSCLC and 1099 CRC patient samples were assayed by PS to evaluate the EGFR or KRAS mutation patterns according to the clinicopathological features. Results The PS assay was able to reproducibly detect as few as 2 % mutant alleles with excellent linearity. EGFR mutations were detected in 35.63 % of the NSCLC samples, and KRAS mutations were detected in 39.76 % of the CRC samples. EGFR mutations were more frequently observed to be significant by multivariate analysis in NSCLC patients who were 65 years old or younger (OR = 2.51), had a nonsmoking history (OR = 3.63), and adenocarcinoma (OR = 3.57), but not in females (OR = 0.64). KRAS mutations were more frequently detected in CRC patients who were female (OR = 1.64) and 50 years old or older (OR = 4.17), and had adenocarcinoma (OR = 2.41). Conclusions This is the first extensive validation of PS on FFPE samples using the detection of EGFR exons 18–21 mutations and KRAS exon 2 mutations. Our results demonstrate the utility of PS analysis for the detection of somatic EGFR and KRAS mutations in clinical samples and provide important clinical and molecular characteristics of NSCLC and CRC from Chinese patients. Electronic supplementary material The online version of this article (doi:10.1186/s13046-015-0179-9) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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