Somatic mutation analysis of EGFR, KRAS, BRAF and PIK3CA in 861 patients with non-small cell lung cancer

Xu, Jianping; He, Jinzhi; Yang, Huiyi; Luo, Xiaodi; Liang, Zhangmin; Chen, Jiaxin; Cai, Zhen; Xu, Jianbing; Ren-Heidenreich, Lifen

doi:10.3233/cbm-2012-0233

Cited by 34 publications

(35 citation statements)

References 34 publications

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“…KRAS mutations were identified in 83 (6.7%) patients, consistent with a previous report (24 smokers, and the elderly, which was also found in the present study. No significant association between KRAS mutations and the presence of GGO/GGN was found, as previously reported (25).…”

Section: Discussionsupporting

confidence: 93%

Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

Zhao¹,

Zhan²,

Li³

et al. 2018

J. Thorac. Dis.

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epidermal growth factor receptor (EGFR) (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (83, 6.7%), human epidermal growth factor receptor 2 (HER2) (82, 6.6%), anaplastic lymphoma kinase (ALK) (23, 1.8%), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) (20, 1.6%), Ret proto-oncogene RET (15, 1.2%), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) (12, 1.0%), B-raf proto-oncogene (BRAF) (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) (3, 0.2%). Fourteen (1.9%) of 731 patients were PD-1 positive and 95 (13.0%) were PD-L1 positive in tumor cells. In men and smokers, there were more frequent KRAS mutations (both P<0.001) and PD-L1 positive tumors (P<0.001, P=0.005, respectively), and less frequent EGFR mutations (P=0.049, <0.001, respectively). In ground-glass opacity (GGO) or ground-glass nodules (GGN), there were more HER2 (P=0.033) but less EGFR (P=0.025) and PIK3CA mutations (P=0.012), and ALK translocations (P=0.014). EGFR (P<0.001), KRAS mutations (P=0.004) and PD-L1 positive tumors (P=0.046) were more frequent in older patients, while HER2 (P<0.001), ALK (P=0.005) and ROS1 aberrations (P=0.044) were less frequent.Invasive mucinous adenocarcinoma was significantly associated with KRAS and ALK aberrations (both P<0.001), while solid predominant adenocarcinoma was associated with ROS1 translocations (P=0.036) and PD-L1 expression (P<0.001). KRAS, HER2, and ALK aberrations were scarce in patients with EGFR mutations (all P<0.001), while PD-L1 positive tumors positively correlated with ALK translocations (P=0.031) and negatively correlated with HER2 mutations (P=0.019). Conclusions: Most patients with primary lung adenocarcinoma harbored target gene aberrations. The frequency of each alteration differed in patients depending on clinicopathologic characteristics.

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Section: Discussionsupporting

confidence: 93%

Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

Zhao¹,

Zhan²,

Li³

et al. 2018

J. Thorac. Dis.

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“…However, there is also evidence that KRAS mutations, which are more prevalent in males, smokers and invasive mucinous ADCs [15,35,38] (fig. 2), are not an a priori negative factor for TKI administration [39].…”

Section: Discussionmentioning

confidence: 99%

EGFR,KRAS,BRAFandALKgene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype

et al. 2013

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Numerous studies have been published on single aspects of pulmonary adenocarcinoma (ADC). To comprehensively link clinically relevant ADC characteristics, we evaluated established morphological, diagnostic and predictive biomarkers in 425 resected ADCs.Morphology was reclassified. Cytokeratin-7, thyroid transcription factor (TTF)1, napsin A, thymidylate synthase and excision repair cross-complementing rodent repair deficiency complementation group-1 expression, anaplastic lymphoma kinase rearrangements as well as epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS) and v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) mutations were analysed. All characteristics were correlated with clinical and survival parameters.Morphological ADC subtypes were significantly associated with smoking history and distinct patterns of diagnostic biomarkers. KRAS mutations were prevalent in male smokers, while EGFR mutations were associated with female sex, nonsmoking and lepidic as well as micropapillary growth patterns. TTF1 expression (hazard ratio (HR) for overall survival 0.61, p50.021) and BRAF mutations (HR for disease-free survival 2.0, p50.046) were found to be morphology-and stage-independent predictors of survival in multivariate analysis. Adjuvant radio-/chemotherapy, in some instances, strongly impacted on the prognostic effect of both diagnostic and predictive biomarkers.Our data draw a comprehensive picture of the prevalence and interplay of established histological and molecular ADC characteristics. These data will help to develop time-and cost-effective diagnostic and treatment algorithms for ADC. @ERSpublications Morphological, diagnostic and predictive biomarkers, and clinical characteristics of pulmonary adenocarcinomas

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“…28 Mutations in PIK3CA are reported in 4% to 5% of NSCLC patients. 15,16,25 Recently, it was shown that the occurrence of PIK3CA mutations in EGFR mutation-positive tumors increases acquired resistance to EGFR-TKIs. 29 However, further research is required to determine the extent to which these mutations may affect treatment.…”

mentioning

confidence: 99%

“…[12][13][14] Mutations in KRAS and other downstream effectors of the EGFR-pathway, such as BRAF and PIK3CA, have also been identified in NSCLC patients. 15,16 KRAS gene mutations are associated with resistance to EGFR-TKIs and occur in 8% to 16% of NSCLCs, which are increased in patients with adenocarcinomas, men, and smokers. 15,[17][18][19][20][21][22] Mutations in BRAF, which are reported in 0% to 3% of NSCLC patients, 15,[23][24][25] predict a clinical response to EGFR-TKIs.…”

mentioning

confidence: 99%

“…15,16 KRAS gene mutations are associated with resistance to EGFR-TKIs and occur in 8% to 16% of NSCLCs, which are increased in patients with adenocarcinomas, men, and smokers. 15,[17][18][19][20][21][22] Mutations in BRAF, which are reported in 0% to 3% of NSCLC patients, 15,23-25 predict a clinical response to 27 It is postulated that mutations in the KRAS, BRAF, and EGFR genes are mutually From the…”

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confidence: 99%

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Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

Emelyanova

Arkhipova

Мазуренко

et al. 2015

Applied Immunohistochemistry &Amp; Molecular Morphology

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Targeted inhibitors of the epidermal growth factor receptor (EGFR) are used for the treatment of non-small cell lung cancer (NSCLC). Somatic mutations in the EGFR gene and key effectors of the EGFR-signaling pathway (KRAS, BRAF, PIK3CA) are associated with sensitivity to these drugs. We developed a highly sensitive LUNG CANCER (LC)-biochip approach for the detection of the most common EGFR, KRAS, PIK3CA, and BRAF gene mutations. The locked nucleic acid clamp PCR technique was used to increase the sensitivity of the assay, then allele-specific hybridization of a fluorescently labeled target on a biochip was performed. To prove the feasibility of the approach, clinical samples from 112 patients with NSCLC were analyzed. A total of 14 EGFR (12.5%) mutations, 21 (18.8%) KRAS mutations, 12 (10.7%) PIK3CA mutations, and 1 BRAF mutation (0.9%) were found. We compared the results with those from direct sequencing. We detected 50 different mutations by the LC-biochip assay and only 33 of them were found by direct sequencing. To demonstrate that the LC-biochip assay did not give false-positive results, the 17 specimens with discordant results were subjected to locked nucleic acid clamp PCR followed by sequencing. The results of this analysis were identical to the results obtained by the LC-biochip assay indicating that the biochip-based assay was both accurate and reliable. This approach was able to detect approximately 0.5% of mutated alleles in wild-type DNA background. The biochip-based assay is a reliable and inexpensive method for the identification of NSCLC patients, who may respond to a specific targeted therapy.

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Somatic mutation analysis of EGFR, KRAS, BRAF and PIK3CA in 861 patients with non-small cell lung cancer

Cited by 34 publications

References 34 publications

Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

EGFR,KRAS,BRAFandALKgene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype

Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

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