EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients

Bae, Nack Cheon; Chae, Myung Hwa; Lee, Myung Hoon; Kim, Kyung Mee; Lee, Eung Bae; Kim, Chang Ho; Park, Tae‐In; Han, Sung Wook; Jheon, Sanghoon; Jung, Tae Hoon; Park, Jae Yong

doi:10.1016/j.cancergencyto.2006.10.007

Cited by 73 publications

(51 citation statements)

References 24 publications

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“…This observation is consistent with other studies showing that the frequencies of KRAS mutations vary with ethnicity [77][78][79][80] . G12D was the most frequent KRAS transition mutation found …”

Section: Dependency Of Ral Activity On Ras Mutationsupporting

confidence: 93%

The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

Guin

Theodorescu

2015

Acta Pharmacol Sin

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Activating RAS mutations are common in human tumors. These mutations are often markers for resistance to therapy and subsequent poor prognosis. So far, targeting the RAF-MEK-ERK and PI3K-AKT signaling pathways downstream of RAS is the only promising approach in the treatment of cancer patients harboring RAS mutations. RAL GTPase, another downstream effector of RAS, is also considered as a therapeutic option for the treatment of RAS-mutant cancers. The RAL GTPase family comprises RALA and RALB, which can have either divergent or similar functions in different tumor models. Recent studies on non-small cell lung cancer (NSCLC) have showed that different RAS mutations selectively activate specific effector pathways. This observation requires broader validation in other tumor tissue types, but if true, will provide a new approach to the treatment of RAS-mutant cancer patients by targeting specific downstream RAS effectors according to the type of RAS mutation. It also suggests that RAL GTPase inhibition will be an important treatment strategy for tumors harboring RAS glycine to cysteine (G12C) or glycien to valine (G12V) mutations, which are commonly found in NSCLC and pancreatic cancer. Review RAS GTPase overviewRAS is the most extensively studied GTPase [1] . It is known to regulate various cellular functions, including proliferation, survival, growth, migration, differentiation and cytoskeletal dynamics [2][3][4] (Figure 1). Not coincidentally, increased activities of all of these processes are required by tumor cells to promote tumor growth. Activating oncogenic RAS mutations lead to treatment resistance in various tumor models and poor patient outcomes [3,[5][6][7][8][9] . Three human RAS genes have been identified: HRAS, KRAS, and NRAS [1,2] . These encode the related proteins HRAS, KRAS and NRAS, respectively, of 189 amino acids in length [1,4] . KRAS exists as two isoforms, 4A and 4B, which are generated by alternative exon splicing [10] . These different RAS genes are well known to have differential cellular specificities and intrinsic transforming potentials [3,4,10] .In normal cells, RAS proteins act as molecular switches for critical cellular functions. RAS proteins are activated by upstream receptors such as receptor tyrosine kinases * To whom correspondence should be addressed. E-mail dan.theodorescu@ucdenver.edu Received 2014-08-07 Accepted 2014-10-30 Figure 1. RAS GTPase activation and downstream signaling. The cartoon shows the mechanism of RAS GTPase activation by upstream stimuli and numerous downstream effectors stimulated by activated RAS. RAS regulates critical cellular functions through these effectors. Constitutive RAS activation due to mutations leads to protumorigenic signaling through these effectors.

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Section: Dependency Of Ral Activity On Ras Mutationsupporting

confidence: 93%

The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

Guin

Theodorescu

2015

Acta Pharmacol Sin

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“…We report here that the frequency of KRAS mutation in 103 NSCLC patients from mainland China is 5.8% (6/103). This result is similar to other countries in Eastern Asia, such as Japan and Korea, where the frequency of KRAS mutation has been reported as less than 10% (19,20). Moreover, the 6 patients with KRAS mutations were all male, which implies that EGFR mutation may be more closely associated than KRAS mutation with the carcinogenesis of NSCLC in East-Asian countries.…”

Section: A C Bsupporting

confidence: 86%

“…However, the variation in mutation frequency between these populations (among patients with NSCLC) for KRAS is contrary to that of EGFR. It was reported that KRAS mutation frequency is about 30% or more in NSCLC patients from the USA and some other Western countries, while it was less than 10% in NSCLC patients from Japan, Korea, Taiwan and Hong Kong in China (1,(15)(16)(17)(18)(19)(20)(21)(22). It is indicated that EGFR and KRAS gene mutations in NSCLC patients may both be dependent on the ethnicity, but the ordering of the mutation frequencies is reversed.…”

Section: Introductionmentioning

confidence: 99%

The status of KRAS mutations in patients with non-small cell lung cancers from mainland China

Liu²,

Liu³

et al. 2009

Oncol Rep

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Abstract. KRAS mutation is closely associated to carcinogenesis and prognosis of non-small cell lung cancer (NSCLC). Detection of KRAS mutation can also be used to select NSCLC patients for drug targeting with EGFR tyrosine kinase inhibitors. Data regarding the status of KRAS mutation in mainland China, which would assist in these interventions, is lacking. We have detected KRAS mutation from 103 NSCLC patients in mainland China with high resolution melting analysis (HRM) on LightScanner™, and compared this method of detection with sequencing, and found HRM to have greater sensitivity. We found 6 patients (5.8%) with KRAS mutation (3 patients, G12C; 1 patient, G12S; 1 patient, G12V; 1 patient, G13D). KRAS mutation was significantly associated to gender (p=0.027) and pathology types (p=0.000), but not to smoking. The mutation frequency of KRAS in NSCLC patients in mainland China is similar to those in East Asian countries, but lower than those in Western countries. However, the spectrum of KRAS mutation in mainland China is similar to those found in the USA. The results also exhibit dependence of KRAS mutation in China on ethnicity. The clinical significance of the spectral pattern of KRAS mutations in TKI resistance or tumorigenesis among patients with NSCLC in mainland China requires further investigation.

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“…However an underlying genetic basis is likely. 5 Oncogenic mutations in EGFR have been found in non-small cell lung cancers in only 19% of African Americans 6-9 and 17% of non-Hispanic whites, 10,11 compared with 66% of Asians [10][11][12][13][14] and 33% of Hispanics. 15,16 Furthermore, EML4-ALK rearrangements are reported in approximately 6% to 7% of Asians with lung adenocarcinoma, compared with only 1% to 2% of non-Hispanic white patients.…”

mentioning

confidence: 99%

Lung Adenocarcinoma Biomarker Incidence in Hispanic Versus Non-Hispanic White Patients

McQuitty

Zhang

Hendrickson

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in nonHispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States.Objective.-To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma.Design.-We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California).Results.-Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested.Conclusions.-Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.

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EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients

Cited by 73 publications

References 24 publications

The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

The status of KRAS mutations in patients with non-small cell lung cancers from mainland China

Lung Adenocarcinoma Biomarker Incidence in Hispanic Versus Non-Hispanic White Patients

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