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Background: Human Lung Carcinoma (LC) is among the most diagnosed cancers across the world among those non-small cell lung cancer (NSCLC) comprises about 85%. Next Generation Sequencing based detection of mutations are now well established in molecular oncology. With the advent of modern diagnostic methods, it is now well known that there are several mutations and gene rearrangements which are associated with the development of LC. Among those mutations, TP53 is the most prevalent with the concomitant EGFR mutation., Methods: In this retrospective study, a total number of 414 patients have been incorporated who have attended RGCIRC in the period between November 2015 to March 2024. Clinical stage has been determined as per NCCN Guideline version 2.2024. Nucleic Acid (DNA and RNA) from FFPE samples were extracted and detection of mutation was performed by Next generation sequencing (NGS) method., Results: All 414 patients opted for the customised NGS panel for lung cancer among those 203 patients were TP53 mutation and 87 patients were EGFR mutation positive. 62 patients were TP53-EGFR double mutation positive. The results of this study have shown that TP53 mutated patients show poor prognosis with conventional therapy. However, TP53-EGFR co-mutated patient's recovery rates are comparatively promising due to the availability of the targeted therapy of EGFR., Conclusion: Studies have shown that TP53 mutation is unlikely to derive clinical benefit in LC patients and shows poorer prognosis when compared to TP53 wild type and EGFR mutated patients show improved recovery due to availability of the Kinase Inhibitor (KI) treatment. In this study we have observed and concluded that TP53-EGFR co-mutated group also shows promising prognosis for the application of KI treatment. A further large cohort study will establish this clinical observation and enlighten more therapeutically relevant information.

Abstract: In-frame fusions in NTRK genes, with intact kinase domain, have been reported to occur at higher frequencies in rare tumors like infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinoma, whereas they occur at very low frequencies in common malignancies like NSCLC and colon cancers (0.1%-1%). Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene. More than 50 fusion partners have been described, and only in-frame fusions result in constitutive ligand-independent kinase activity leading to oncogenesis. The commonly reported NTRK fusions in the lung include SQSTM1-NTRK1, ETV6-NTRK3, and SQSTM1-NTRK3. Detection of these rests on the use of conventional modalities like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however, accurate characterization requires direct sequencing methods. We report an interesting case of an NTRK fusion-positive NSCLC, exhibiting good response to entrectinib., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: KRAS, although a common variant of occurrence (~20% of non-small-cell lung carcinoma [NSCLC]) has been untargetable, owing to the molecular structure which inherently prevents drug binding. KRAS mutations in NSCLC are associated with distinct clinical profiles including smokers and mucinous histology. KRAS G12C mutations account for ~40% KRAS altered NSCLC, but NSCLC being a geographically diverse disease, the features may be distinct in this part of the world. This is a single-center experience of KRAS-mutated NSCLC including clinical, imaging, pathologic features, and treatment patterns and outcomes., Methods: This is a single-center retrospective study of KRAS-mutated NSCLC. The clinicopathological features and outcomes were retrieved and collated from the medical record archives of the hospital., Results: Fifty (30.6%) patients with advanced-stage NSCLC with alterations in the KRAS gene were enrolled in the 163 patients who were tested for KRAS alterations. The median age was 61 years. Molecular detection revealed three main types of KRAS mutations viz-a-vis: G12C in 17 (34%), G12V in 9 (18%), and G12D in 6 (12%) patients. Comparing G12C versus the non-G12C mutated cases, co-mutations were common in the non-G12C subgroup (p < 0.05). Among the 36, who were treated at our center, all received chemotherapy as the first line with a median progression-free survival (PFS)of 5.4 months. The PFS of G12C was higher than the non-G12C subgroup (6.4 vs 3.8 months)., Conclusion: This is the largest single-center experience from the Indian subcontinent for KRAS-mutated NSCLC with distinct clinical features. It highlights the unmet need for G12C inhibitors in our country, where prevalence is equivalent to the West., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: Anaplastic lymphoma kinase ( ALK ) rearranged non-small cell lung carcinoma (NSCLC) is a distinct molecular subtype and rapid approval of ALK tyrosine kinase inhibitors (TKIs) has necessitated rapid and sensitive diagnostic modalities for the detection of this alteration. Gene rearrangements can be identified using many techniques including fluorescence in situ hybridisation (FISH), reverse transcriptase-PCR, next-generation sequencing (NGS) and immunohistochemistry (IHC) for fusion oncoprotein expression. We aimed to determine the concordance between IHC, FISH and NGS for ALK biomarker detection, and determine differences in sensitivity, and survival outcomes., Methods: We analysed the concordance between IHC using D5F3 monoclonal antibody, FISH (break-apart) and NGS using a custom panel containing 71 different ALK variants., Results: Among 71 cases included in this study, FISH was evaluable in 58 cases. The concordance of ALK IHC with FISH was 75.9% and that with NGS was 84.5%. The sensitivities of FISH and NGS were 75.6% and 87.5%, respectively. The median progression-free survival of ALK IHC-positive and FISH-negative group was 5.5 months and that of both positive was 9.97 months., Conclusion: Although NGS offers a better throughput and visualisation, IHC still remains the quintessential screening tool in upfront diagnosis of ALK rearranged NSCLC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The emergence of sophisticated next generation sequencing (NGS) based technologies in routine molecular diagnostics has paved the way for robust and accurate detection of variants which may otherwise be missed on single gene testing. This study aims at highlighting the same premise in EGFR mutated non-small cell lung carcinoma (NSCLC)., Methods: 1350 cases of NSCLC were screened, of which 490 EGFR mutated cases were taken. The clinical records and molecular features were evaluated retrospectively to determine those cases which were missed on single gene testing., Results: Among these 490 cases, there were 11 (2.2%) cases which tested negative on single gene testing using polymerase chain reaction (therascreen). These were then subjected to NGS based testing and were positive for 13 different EGFR mutations. Five out of the 11 cases received EGFR tyrosine kinase inhibitor (TKI) based on the NGS test outcome. Four cases with exon 20 insertion mutations were not offered TKI as these mutations are known to be intrinsically resistant to TKI therapy. The five patients who have been treated with TKI have shown fair response and have not progressed to date., Conclusions: We demonstrated a potentially preferable way to profile treatment-naïve patients with NSCLC by NGS and from our early experience in EGFR mutant cases, the advantages of NGS over single gene testing is clearly evident., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. Methods: 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019-2020. Results: Of 184 cases, 70 were positive by Cobas, 51 by ddPCR and 69 by Therascreen. The sensitivity of Cobas was 97.1% and the sensitivity of ddPCR was 71%. Receiver operating characteristic analysis showed an area under the curve of 0.977 for Cobas and 0.846 for ddPCR. Conclusion: In line with the FLAURA trial of osimertinib making its way to first-line and given the IASLC recommendations, it is important to understand the attributes of these tests to initiate appropriate treatment.

Background: Cell free DNA (cfDNA) shed by cancer cells into blood and body fluids is a potential substrate for molecular testing. While plasma is approved for EGFR mutation testing in certain clinical settings, mutation testing on urine is not well explored in lung cancer. In this study, we assess the feasibility and diagnostic accuracy of EGFR mutation analysis on plasma and urine samples., Methods: Matched plasma and urine were collected prospectively from TKI-naïve lung adenocarcinoma (ADCA) patients (Group A) with available tumor tissue. Only plasma was collected from TKI-treated, known EGFR mutant ADCA patients developing TKI resistance (Group B). qPCR (tumor tissue) or digital droplet-PCR (urine/plasma) was performed for exon 19 deletions, exon 21 L858R and exon 20 T790M., Results: Eighty-one patients (60 Group A, 21 Group B) were included. In Group A, EGFR mutations were detected in tissue in 34/60 (57%) patients. Mutations were detected in matched plasma in 24 (24/34, 70.5% sensitivity), and in matched urine in 15 (15/25, 60% sensitivity) of the 34 EGFR mutant cases, with no false positives (100% positive predictive value). Plasma and urine mutation results showed moderate agreement (70%) with a combined sensitivity of 88% (22/25). In Group B, new T790M mutations were detected in plasma in 61% (13/21) patients., Conclusion: Liquid biopsies show moderate sensitivity (plasma > urine) with 100% positive predictive rates for EGFR mutations. Testing of more than one type of liquid biopsy sample increases sensitivity. In TKI-resistant settings, liquid biopsies can obviate need for invasive biopsies in >60% patients., (Copyright © 2021. Published by Elsevier Inc.)

Activating mutations in the KRAS gene (Kirsten rat sarcoma 2 viral oncogene homolog gene) are commonly seen across the various solid organ and hematolymphoid neoplasms. With the likelihood of the mutation specific KRAS inhibitor entering clinical practice, the present studies profiled the landscape of these mutations in the Indian population to add to databases and posit the clinical utility of its emerging inhibitors. This study included 489 formalin fixed paraffin-embedded (FFPE) tissue samples from consecutive patients during a 5-year period (2015-2019). The clinical records were obtained from the medical record archives of the institution. Library preparation was done using the Oncomine Assay™. Sequencing was performed using the Ion PGM Hi-Q Sequencing Kit on the Ion Torrent Personal Genome Machine (Ion PGM) as well as on Ion Torrent S5 sequencer using the S5 sequencing kit. Ion Torrent Suite™ Browser version 5.10 and Ion Reporter™ version 5.10 were used for data analysis. A total of 50 cases with KRAS mutations were observed occurring most commonly in the codons 12 and 13. The G12D mutation was the most commonly encountered subtype in our cohort (21/50), whereas the G12C mutation was observed in 5 cases, and interestingly, this mutation was only seen in patients with non-small cell lung carcinoma (NSCLC). In the largest cohort from Indian subcontinent reporting spectrum of KRAS mutations in human cancers, an incidence of 11% was observed across all cancer types. Therapies targeting the G12C mutations can benefit up to 20% KRAS-mutated NSCLC. Building databases of spectrum of KRAS mutations in different populations across diverse cancer types is the anticipatory step to this end.

Background: Reliable blood markers for aiding lung cancer (LC) diagnosis and differentiating LC from tuberculosis are lacking in India., Methodology: In this single-centre, cross-sectional, real-world study, serum levels of 5 TMs (CEA, CYFRA 21-1, SCC, ProGRP, NSE) were measured from consented patients with suspicious lung nodules who were candidates for biopsy, and also from healthy controls. TM level measurement was done through electrochemiluminescent immunoassay, followed by histological diagnosis on the biopsied specimen. Using package insert cut-offs, sensitivity and specificity of the 5 TMs were evaluated individually and in combination. Using receiver operating characteristic (ROC) curves of individual TMs, the ability of CEA, CYFRA 21-1, and ProGRP taken together was evaluated for its ability to differentiate LC from no-LC., Results: Out of 178 subjects, 160 had LC (147 NSCLC; 13 SCLC). NSCLC patients had higher median values of CYFRA 21-1 and SCC; SCLC patients had higher median values of CEA, NSE, and ProGRP. Adenocarcinoma-NSCLC patients had higher median values of CEA, CYFRA 21-1, NSE, and ProGRP; squamous-NSCLC patients had higher median value of SCC. For differentiating LC from no-LC, the combination of all 5 TMs (sensitivity:97.5%, specificity:33.3%) and combination of CEA, CYFRA 21-1 and ProGRP (sensitivity:91.3%, specificity:88.9%) were found suitable., Conclusion: Combination of all 5 TMs, and combination of CEA, CYFRA 21-1, and ProGRP represents an easy and non-invasive method for aid in LC diagnosis that does not require technical expertise. TM evaluation can also supplement histological diagnosis of LC. , .

Anaplastic lymphoma kinase (ALK) rearranged NSCLC comprises a molecularly distinct subgroup occurring in 10% cases. Various EML4-ALK and non EML4 variants are known to occur which can be detected only on NGS and show differential TKI responses. 113 ALK-IHC positive cases were subjected to a custom panel-based NGS for detection of ALK variants. Clinicopathologic features and outcomes were studied and propensity-matched analysis was done. The median age of the overall cohort was 53 years. 91 (80.5%) cases were NGS positive, the most common being EML4-ALK (90, 98.9%) cases. The most common EML4 variant was Variant 1 (40, 35%) cases, Variant 3 (28, 25%) cases, and Variant 2 (17, 15%) cases. One novel EML4-ALK variant was also encountered which was found to be intrinsically resistant to crizotinib. On pre-weight-adjusted comparison, Variant 1 group had a higher occurrence of brain and extrathoracic metastases. The median OS was 44 months for the entire cohort. 49 patients received crizotinib as first-line TKI. Among these, the median OS for Variant 2 was not reached; it was 38 months and 24 months for Variant 1 and Variant 3, respectively. The median PFS for crizotinib treated patients was 8.3 months (Variant 2: 11 months, Variant 1: 8 months, and Variant 3: 9 months). On propensity-matched analyses, there was no difference in OS and PFS between Variant 1 and Variant 3, with higher HR for Variant 3. We present a large data set evaluating clinical and outcome differences between ALK variants. The unique standpoint of this study involves the propensity-weighted model to account for differences among the groups, with no prognostic differences between Variant 1 and Variant 3, which is distinct from literature.

Introduction: EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35-40% of cases in the Asian NSCLC cohort, compared to 15-20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used. Preclinical studies have reported that PDL1 (programmed death ligand 1) is a downstream target of EGFR and is interposed by IL-6/JAK/STAT3 (interleukin-6/Janus kinase/signal transducer and activator of transcription 3), NF-κB (nuclear factor kappa beta), and p-ERK1/2/p-c-Jun pathways. Hence, it may potentially be repressed by EGFR TKIs. In this retrospective exploratory analysis, we studied whether PDL1 expression affects efficacy of EGFR TKIs and clinical outcome in patients with untreated metastatic EGFR-mutated lung adenocarcinoma., Methods: This single-center retrospective, exploratory analysis was performed between January 2015 and December 2019. Among 1350 cases of NSCLC, 470 were EGFR mutant, of which PDL1 expression testing was done in 193 patients who were included in this study., Results: Median age was 60 years (range 24-87 years). A total of 116 patients (60.1%) had inframe deletion in exon 19, 52 (26.9%) had L858R, and 25 (13%) had uncommon mutations. The number of patients with PDL1 tumour proportion score (TPS) < 1% was 109 (56.5%); 1-49%, 57 (29.5%); and ≥ 50%, 27 (14%). Comparing clinical characteristics among various PDL1 groups, there were no statistically significant correlations obtained. However, patients with PDL1 > 50% were smokers, and showed a trend for higher disease burden at diagnosis. Median PFS of PDL1 < 1% was 10.14 months, compared to 9.4 months in the PDL1 > 1% group; however, the values did not reach statistical significance., Conclusion: The current study was an exploratory retrospective study; however, the results add to the growing body of evidence that PDL1 expression in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.

Aims: The present study investigated the incidence and spectrum of human epidermal growth factor receptor 2 (HER2) mutations, associated clinicopathological characteristics and the co-occurrence of HER2 gene amplification in the HER2 gene mutated cases in non-small cell lung cancer (NSCLC)., Methods: All patients with advanced lung adenocarcinoma (LUAD) who underwent broad genomic profiling by next generation sequencing (NGS) from 2015 to 2019 were included in the study. HER2 gene amplification was checked in all the HER2 gene mutated cases. Tumour tissues of all the mutated cases were examined by fluorescent in situ hybridisation (FISH)., Results: Fifty-four (37.2%) out of the 145 cases harboured tier 1 driver mutations comprising EGFR in 22.1%, ALK rearrangements in 7.6% cases, ROS1 rearrangements and BRAF V600E in 3.5% cases each, and NTRK fusion in 0.7% cases. Nine (6.2%) cases exhibited a significant genetic alteration in HER2 gene (tiers 2 and 3) on NGS. The most common alteration was exon 20 insertion of amino acid sequence AYVM in five cases (p.E770&#95;A771insAYVM) followed by insertion of YVMA (p.A771&#95;Y772insYVMA) in one case, insGSP (p.V777&#95;G778insGSP) in one case and two missense mutations: p.G776C and p.QA795C (novel variant). The median copy number of the HER2 gene was 3.21 while on FISH, the median HER2/CEP17 ratio was 2.0., Conclusions: There is a relatively higher occurrence of HER2 exon 20 mutations as primary oncogenic driver in NSCLC especially LUAD. Our cohort has demonstrated (p.E770&#95;A771insAYVM) as the strikingly dominant insertion mutation against the most often globally reported (p.A771&#95;Y772insYVMA)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The predictive value of rare epidermal growth factor receptor gene (EGFR) mutations for non-small cell lung carcinoma (NSCLC) patients remain elusive. We evaluated the distribution, clinicopathological association, tyrosine kinase inhibitor (TKI) response, and outcome of NSCLC patients carrying uncommon EGFR aberrations in comparison to classical EGFR mutations., Methods: Treatment naïve, advanced NSCLC cases tested by Next-Generation sequencing (NGS) method between 2015 and 2020 were included. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed., Results: A total of 237 tumor samples were sequenced. Among the sixty-nine (29%) EGFR mutated cases, 41 (59.4%) harbored classical mutation (37.7% Del19, 21.7% p.L858R). Non-classical aberrations included missense mutations in exon 18/20/21 (15.9%), EGFR amplification (8.7%), exon 20 insertions (7.2%), EGFR Variant III (4.3%), exon 18 indel (2.9%), exon 21 missense (2.9%) and exon 19 missense mutation (1.4%). These occurred as complex mutations in 16% of cases. Oral TKI was administered in 66.7% cases. The patients harboring non-classical variants had a lower ORR and DCR (23.1% and 61.5%) than those carrying a common mutation (57.6% and 84.8%). Collectively, compared to the patients with common EGFR mutations, the uncommon group showed early disease progression and had shorter overall survival., Conclusion: NGS testing has the capacity to reveal a diverse spectrum of uncommon EGFR variants. Our study can contribute to the database of uncommon EGFR mutations with a positive influence on evidence-based care of advanced lung cancer patients with EGFR mutations., (Copyright © 2021. Published by Elsevier Ltd.)

Myoepithelial tumor of lung is a rare tumor; the histopathological findings resemble the myoepithelial tumors of the salivary gland. Distinguishing low-grade nonmetastatic myoepithelial carcinoma from benign myoepithelioma can be challenging both radiologically and histomorphologically. We present a case report of a low-grade myoepithelial carcinoma of lung with contralateral lung metastasis which was treated with low-dose external beam radiotherapy.

Hepatoid adenocarcinoma of lung is a rare entity, accounting for 5% of all hepatoid adenocarcinoma. Distinguishing it from metastatic hepatocellular carcinoma is essential, but occasionally can be very challenging, especially with concurrent liver mass. A judicious immunohistochemical panel is warranted for accurate diagnosis and subsequent preservation of tissue for molecular testing. There is limited data on the mutational status, behavior and management strategies of this type of lung adenocarcinoma. We report largest series of six cases of hepatoid adenocarcinoma of lung citing the clinical, histopathological, immunohistochemical and molecular parameters including PD-L1 immunoexpression as a predictive biomarker for immunotherapy. None of the evaluated cases showed targetable mutation; however, four out of six cases showed significant PD-L1 expression. All the cases presented with advanced stage and received chemotherapy, however overall prognosis was dismal. In view of significant PD-L1 expression in these tumors and poor response to conventional chemotherapy, these cases might be considered for upfront immunotherapy., Competing Interests: None

Tag-sequencing is a modified next-generation sequencing (NGS) approach wherein targeted regions are tagged with unique molecular identifiers enabling error-free detection of rare genomic alterations. We aimed to perform this high- fidelity sequencing to identify actionable variants from the plasma of lung cancer patients. Targeted sequencing was performed from plasma-derived cell-free nucleic acid in twenty-one advanced, treatment naïve, non-small-cell lung cancer (NSCLC) patients. Clinically significant genetic alterations were compared with matched tumor NGS profile for each patient (patient-level), and separately for each alteration (variant-level). Cross-platform validation was done for EGFR and KRAS mutations (real-time PCR) and ALK1 rearrangement (immunohistochemistry). Forty-seven alterations (26 in plasma and 21 in tumor tissue) were detected in 19/21 tested cases. Overall-concordance between the two assays was 94.87% (κ of 0.71, 95% CI: 0.54-0.89). Patient-level and genic-concordance was 57.1% (12/21 cases) and 67.86%, respectively. Almost perfect agreement was reached for detecting actionable EGFR mutations and ALK1 rearrangement (κ of 0.89 and κ of 1, respectively), which was confirmed by single-gene testing. Substantial agreement between the assays makes Tag-sequencing a viable option for identifying multibiomarkers from the plasma of advanced NSCLC patients in special circumstances where tissue has depleted/tumor is inaccessible/high risk of biopsy due to existing comorbidities.

Background: EGFR mutant NSCLC patients have leptomeningeal (LM) involvement in more than 9% cases., Material & Methods: We conducted a study evaluating the diagnostic utility of cfDNA EGFR testing in CSF using DdPCR while comparing it against MRI and CSF cytology. We also looked for known EGFR mutations in the CSF sample. These mutations were also tested in paired plasma samples. We further compared which constituent of CSF (pellet/supernatant) had better yield., Results: 21 patients comprised the study. Of these 17 patients were diagnosed to have LM involvement based on conventional criteria. All modalities had 100 % specificity and positive predictive value. However, MRI and CSF cytology had a poor negative predictive value. cfDNA had the highest sensitivity (92.3 %), negative predictive value (75 %), accuracy (94.1 %), and net comparative benefit. Paired plasma samples were available for 19 patients. Primary EGFR mutation was detectable in the CSF sample in 16/19 patients; however, the plasma sample was positive only in 7/19 patients. 3 samples were negative for primary EGFR mutation in both CSF and plasma. None of the CSF samples showed positivity for T790M mutation which could however be observed in two patients in plasma samples. Both supernatant and pellet were analysed for cfDNA mutation analysis in 18/21 patients. The intraclass correlation coefficient regarding the percentage fraction tumor-derived DNA of cfDNA observed was 0.83(95 % CI 0.29 to 0.95) between both samples., Conclusion: EGFR detection in CSF has a potential role in diagnosing LM involvement. T790 M resistance mutations are uncommon in CSF post first and second-generation TKIs. Both supernatant and pellet samples can be used for the extraction of cell-free DNA in CSF., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The presence of activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in adenocarcinomas of lung confers sensitivity to tyrosine kinase inhibitor therapy. The prevalence of EGFR mutations varies among different ethnicities and demographic profile. This multi-institutional data was compiled to determine the EGFR mutation status in Indians patients with lung adenocarcinoma. Cohorts represented by 4 tertiary care hospitals participated in data discussion at a national conference entitled as 'Lung Cancer Management in Indian Context'. The clinicopathologic data and EGFR mutation rate in the patients of lung adenocarcinoma screened in these cohorts were collected and analyzed. The sample types included both surgical and cytological specimens. A variety of methods were used including immunohistochemistry, polymerase chain reaction, Sanger sequencing and next generation sequencing. A total of 3436 cases of treatment naïve lung adenocarcinoma were tested for EGFR mutations. The overall frequency of EGFR mutations observed was 30.03%. The most common baseline mutation detected was exon 19 deletion followed by L858R point mutation in exon 21. Dual mutations were observed in 6.5% of cases and were predominantly combinations of exon 19 deletion and T790M point mutation in exon 20. Incidence of EGFR mutations was higher among females and non-smokers diagnosed with lung adenocarcinomas. The most common histology in EGFR mutant cases was acinar predominant adenocarcinomas. With nearly one-third of Indian patients with lung adenocarcinoma harboring EGFR mutations, routine testing for these mutations is important to get the benefit of targeted therapy., (Copyright © 2020. Published by Elsevier Inc.)