Molecular Spectrum of Somatic EGFR and KRAS Gene Mutations in non Small Cell Lung Carcinoma: Determination of Frequency, Distribution Pattern and Identification of Novel Variations in Indian Patients

Das, Bibhu Ranjan; Bhaumik, Sangeet; Ahmad, Firoz; Mandsaurwala, Aziz; Satam, Heena

doi:10.1007/s12253-014-9874-7

Cited by 16 publications

(10 citation statements)

References 68 publications

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“…The percentage of BRAF mutation in NSCLC observed across the globe varies from 0.4% to 4.9% in the Western countries 16,18 to 0.3% to 1.9% in Asia. 7,22–24 Our findings are in concordance with global data. The targetable mutations which have been identified are BRAF L597V and V600E point mutations.…”

Section: Discussionsupporting

confidence: 91%

“…16–18 In Asian countries, the range is much lower and constitutes only 3% to 19% in all NSCLCs. 9,10,19–23 Two previous studies from India, both from the same center have revealed lower frequencies of KRAS positivity of 6.4% and 1.5% respectively 7,24 ; as compared to 19.5% in the present study. The primary reason for this variation can be attributed to the method of detection of the mutation and higher prevalence of smokers in this cohort.…”

Section: Discussioncontrasting

confidence: 51%

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Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Singh

Guleria

Malik

et al. 2019

Current Problems in Cancer

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Mitogen-Activated Protein (MAP) Kinase pathway involves several oncogenic genes which can serve as potential targets for therapy. Therefore, aim of the present study is to analyze mutations in the MAP Kinase pathway in pulmonary adenocarcinoma (ADCA) of Indian patients along with clinico-pathologic correlation and determination of the survival status in patients receiving therapy. Blocks and slides of 125 pulmonary ADCA of last 5 years were retrieved. Histo-morphology and tumor content were determined. EGFR, KRAS, BRAF and MEK1 genes were analyzed using Sanger sequencing and Real-time polymerase chain reaction (PCR). Clinico-pathologic correlation and survival analysis were performed. Fifty-eight (46.4%) patients harbored genetic mutations of which 49 had single somatic mutations, 5 had multiple exonic and 4 showed coexisting EGFR and KRAS mutations. EGFR mutations were seen in 24.8%, KRAS in 19.2% and BRAF (non-V600E) in 2.4% cases. There was no difference in progression-free survival of wild- type/single mutations when compared with multiple/ coexisting mutations (P = 0.09). However, the P value may indicate borderline correlation. To conclude, EGFR and KRAS mutations may coexist in the same patient in lung ADCA. Multiple exonic mutations of KRAS gene formed substantial percentage of our cohort, requiring further exploration. Lung ADCA harbouring BRAF mutations are commonly non-V600E. Testing of all major genetic driver mutations of lung ADCA irrespective of histology and other demographic characteristics is necessary.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 51%

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Singh

Guleria

Malik

et al. 2019

Current Problems in Cancer

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“…Liquid biopsy, a noninvasive method which assesses the genetic makeup of a tumor through a biofluid sample, has the potential to help clinicians screen for disease as well as monitor treatment response and resistance mechanisms in the tumor. [26] The results of our study are in line with the global trend with the incidence of EGFR mutation higher in females (32.5%), nonsmokers (30.6%), adenocarcinoma (24.9%), and Stage IV disease (23.7%). Chougule et al reported the prevalence (23.2%) of EGFR mutation in a sample size of 907 patients.…”

Section: Discussionsupporting

confidence: 89%

Feasibility of molecular testing in a multicenter study with geographical variation in India: Epidermal growth factor receptor mutation as a model molecular test

Prabhash

Rauthan

Rajappa

et al. 2017

Asian Journal of Oncology

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Context: Trends in epidermal growth factor receptor (EGFR) mutation based on ethnicity assist the initial selection of targeted therapy regimen. Reported incidence of EGFR mutation in Indian NSCLC patients is variable, ranging from 22% to 51.8%.Aim and Settings and Design: This multicenter, noninterventional study evaluated the prevalence of EGFR mutation in Indian NSCLC patients, its association with patients’ demographics, and for the first time used a central laboratory for molecular testing.Subjects and Methods: Tissue samples from 252 NSCLC patients were tested at a Central Laboratory at Tata Memorial Hospital. Statistical Analysis Used: Patient demographics, baseline characteristics including smoking status from routine examination were recorded in a single visit. Chi-square or Fisher's exact test was used for association of EGFR mutation status with gender, age, smoking status, and histological subtypes.Results: The prevalence of EGFR mutation in Indian NSCLC patients was 23.4%. Among these, 55.9% patients had mutations in exon 19, 39% in exon 21, and 1.7% in exon 18. The incidence of EGFR mutation was higher in females than males (32.5% vs. 18.9%, respectively), and in 30.6% patients that had never smoked, 26.3% smokers, and 5.8% former smokers. The mean duration of transportation of tissue samples to the central laboratory was 48 h with an average turnaround time of 5 days for molecular testing.Conclusions: Molecular testing at a central laboratory is a feasible option in India. Prevalence of EGFR mutation in Indian NSCLC patients was similar across western and southern centers in India. A statistically significant association between EGFR mutation and gender as well as the smoking status of the patients was observed. Majority of the patients had in-frame deletions in exon 19.

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“…According to this pathological-radiological correlation, the majority of AIS and MIA cases corresponded to pGGO, while IAC cases corresponded to sGGO. EGFR and KRAS mutations are two of the most common mutations in NSCLC (29,30). The presence of EGFR mutations is a critical biological determinant for adequate therapy selection in patients with lung cancer (31).…”

Section: Discussionmentioning

confidence: 99%

Impact of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of stage IA adenocarcinoma of the lung: Correlation between computed tomography images and EGFR and KRAS gene mutations

Wang

Zhang

Han

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to compare pathological diagnoses, as determined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, with conventional radiological features. In addition, the present study aimed to evaluate the correlation among clinical characteristics, computed tomography (CT) images and gene mutation status in patients with stage IA adenocarcinoma of the lung. A total of 212 patients with stage IA lung adenocarcinoma were included in the study. The patients were classified into pure ground-glass opacity (pGGO), mixed GGO (mGGO) and solid GGO (sGGO) by CT imaging. Histological subtype was classified according to the IASLC/ATS/ERS classification of lung adenocarcinoma. In addition, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) mutation assays were performed, and 36.8% of patients (78/212) were determined to have an EGFR mutation, while 8.5% of patients (18/212) were found to have a KRAS mutation. According to the IASLC/ATS/ERS classification, 44 cases were diagnosed as adenocarcinoma in situ (AIS; 20.8%), 62 cases were diagnosed as minimally invasive adenocarcinoma (MIA; 29.2%) and 106 cases were classified as invasive adenocarcinoma (IAC; 50.0%). pGGO image patterns were observed in 39.2% of patients (n=83), while mGGO and sGGO patterns were observed in 28.8% (n=61) and 32.0% (n=68) of patients, respectively. From pGGO to sGGO, cases of AIS and MIA were shown to have a decreasing trend, while IAC cases exhibited an increasing trend (P=0.036). Analysis of the correlation between CT image patterns and gene mutations demonstrated that L858R point mutations, exon 19 deletions and KRAS mutations were more common in lesions with a lower GGO proportion (P=0.029, 0.027 and 0.018, respectively). Therefore, according to the IASLC/ATS/ERS classification, GGO imaging patterns were shown to correlate with subtypes of adenocarcinomas. In addition, EGFR and KRAS mutations were found to be associated with lesions with a low GGO proportion. Therefore, analysis of GGO lesions may offer useful indications of the histological subtype of an adenocarcinoma in patients with stage IA lung adenocarcinoma, and predictive value for EGFR and KRAS mutations.

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Molecular Spectrum of Somatic EGFR and KRAS Gene Mutations in non Small Cell Lung Carcinoma: Determination of Frequency, Distribution Pattern and Identification of Novel Variations in Indian Patients

Cited by 16 publications

References 68 publications

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Feasibility of molecular testing in a multicenter study with geographical variation in India: Epidermal growth factor receptor mutation as a model molecular test

Impact of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of stage IA adenocarcinoma of the lung: Correlation between computed tomography images and EGFR and KRAS gene mutations

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