Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center

Assi, Hazem; Tfayli, Arafat; Assaf, Nada; Daya, Sarah Abou; Bidikian, Aram; Kawsarani, Dima; Fermanian, Puzant; Zaatari, Ghazi; Mahfouz, Rami

doi:10.1007/s11033-019-04797-5

Cited by 6 publications

(7 citation statements)

References 21 publications

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“…It can either occur as a primary mutation or as an acquired mutation following the TKI treatment. The T790M mutation can be as high as~50% in patients treated with TKIs, whereas the treatment-naive mutations are reported to be less than 1% [28,29]. This mutation almost always coexists with either the Exon 19 deletion or the L858R mutation.…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico

Zheng

Yin

Alhatem

et al. 2020

Cancers

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Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

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Section: Discussionmentioning

confidence: 99%

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico

Zheng

Yin

Alhatem

et al. 2020

Cancers

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“…There are studies showing that the T790M mutation in EGFR exon 20 is associated with Tyrosine Kinase Inhibitor (TKI) resistance. In a study conducted, when the cases with TKI resistance or relapsing diseases were examined, it was seen that 50% of these cases had the T790M mutation (14). There are studies linking acquired resistance to afatinib with the T790M mutation, and it has been stated that osimertinib treatment may be an option in patients who develop resistance (15).…”

Section: Discussionmentioning

confidence: 99%

“…The DNAs obtained were examined in terms of point mutations at Erciyes University Genome and Stem Cell Center (GENKOK) using the new generation sequencing commercial kit 56G Oncology Panel. With 56G Oncology Panel EGFR (3,7,15,(18)(19)(20)(21), CDKN2A (2), DNMT3A (23), DDR2 (18), TP53 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), ABL1 (4-7), FGFR2 (5,7,8,11), AKT1 (3.6), NOTCH1 (26,27,34), ALK (23.25), APC (14), FGFR3 (7,9,12,14,16), ATM (8,9,12,17,26,(34)(35)(36)39,50,5456,6163), BRAF (11,15), STK11 (1,4,6,8), CDH1…”

Section: Sample Collection and Studymentioning

confidence: 99%

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The Effect of Mutations Determined by Liquid Biopsy on the Progress of the Disease in Advanced Lung Adenocancer

Ergin¹

2022

Erciyes Med J

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“…Recent studies have con rmed that EGFR mutations from plasma can predict the clinical response to targeted therapy [95,96]. In the MENA region, the T790M mutation, using liquid biopsy, has been conducted only in NSCLC patients from Lebanon [97]. In addition, Next Generation Sequencing (NGS) has the ability to detect the whole exome or genome and is not restricted to speci c target sequences.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Patterns of EGFR Mutations in Non-Small Cell Lung Cancer in the Middle East and North Africa: A Systematic Review

Boustany

Laraqui

Rhaffouli

et al. 2021

Preprint

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To summarize current evidence and estimate the prevalence of epidermal growth factor receptor (EGFR) mutation frequency and its association with ethnicity and clinic-pathological features in non-small cell lung cancer (NSCLC) patients in the Middle East (ME) and North Africa (NA), a systematic literature review was undertaken. We conducted a literature search of original articles published in six databases (PubMed, Science Direct, Web of Science, Embase, Scopus, and Google scholar) from the time of inception until April 2021. Search terms included “lung cancer”, “NSCLC”, “EGFR mutation”, “Middle East”, “North Africa”, and specific country names belonging to the considered region. The included studies had to meet the following criteria: the study must relate to the role of the EGFR gene in NSCLC, analyze mutations in exon 18, 19, 20, and 21 or select exons of the EGFR gene, and provide sufficient information on the clinic-pathological characteristics of the included NSCLC patients. A total of 24 eligible studies were included [(66.6%) in the ME and (34.4%) in NA]. Overall, 6544 patients with NSCLC were analyzed for EGFR mutations [(55.1%) in the ME and (44.8%) in NA]. The overall prevalence of EGFR mutations was 17.9%. In the ME, the reported frequency was 17.3%, whereas in NA, the prevalence of EGFR mutations was 18.5%. The most frequently encountered mutations were the exon 19 deletions (45.2%) and exon 21 substitutions (30.9%). Exon 20 alterations were detected in 11.2%, of which, the T790M resistance mutation was the most prevalent (45.5%). Exon 18 mutations were reported in 3.8%. In the ME, 50.5% of NSCLC patients were positive for exon 19 deletions versus 48.3% in NA. Exon 21 mutations were slightly more commonly detected in the ME (36.3%) than NA (31.3%). There was 1.2% of patients that had concurrent EGFR mutations. Overall, EGFR mutations prevalence was higher in females, non-smokers, and patients with adenocarcinoma. Our systematic literature review concurs that EGFR mutation prevalence among MENA populations is slightly higher than that seen in NSCLC patients of Caucasian ethnicity but is lower than that identified in Asian NSCLC patients. The distribution of these mutations varies significantly throughout the MENA region.

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Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center

Cited by 6 publications

References 21 publications

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico

The Effect of Mutations Determined by Liquid Biopsy on the Progress of the Disease in Advanced Lung Adenocancer

Prevalence and Patterns of EGFR Mutations in Non-Small Cell Lung Cancer in the Middle East and North Africa: A Systematic Review

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