Prevalence of the EGFR T790M and other resistance mutations in the Australian population and histopathological correlation in a small subset of cases

Kim, Roger H.; Lapuk, Anna; Harraway, James; Lee, Eric; Walsh, Michael D.; Topkas, Eleni; Jones, Victoria; Burn, Julie; Baillie, Tina; Lim, Cathy; Nejad, Kambin; Muljono, Anita; Gagné, Éric; McConechy, Melissa K.; Zein, Yesser; Maclean, Fiona; Gill, Anthony J.; Vargas, Ana Cristina

doi:10.1016/j.pathol.2020.03.003

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…In the case of our K757N mutation, there are only several mentions of this variant in the literature to date, none of which directly link the mutation to any clinical significance. A retrospective mutational testing study from Australia reported that the K757N mutation was only found in 2/514 (0.4%) patients reviewed with a confirmed EGFR mutation [6]. There have been only 2 cases reported in the literature which include outcomes with TKI therapy for patients with a K757N mutation.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report

2022

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Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing mutations respond well to targeted therapy, the relevance of germline EGFR mutations is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell lung cancer. Familial history for lung cancer is negative. Targeted next-generation sequencing on the tumor biopsy sample revealed an atypical EGFR K757N mutation at 50% allele frequency and genetic review of a previously acquired gastric sample confirms the mutation as a germline change. He received standard first-line chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab, and after 8 months therapy continues, with stable disease, to receive maintenance pemetrexed and pembrolizumab. To our knowledge, this is the first report of an atypical, germline K757N EGFR mutation. While the clinical relevance of this mutation is unclear, standard reporting of the allelic frequency of novel, atypical mutations can detect potential germline changes.

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Section: Discussion/conclusionmentioning

confidence: 99%

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report

2022

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Section: Lung Cancer In Oceaniamentioning

confidence: 99%

“…In the few reported series, the frequency of EGFR mutations in the Australian population with lung cancer ranges between 19% and 28%, 161 – 165 including T790M mutations (9.3%) and exon 20 insertions (4.8%). 165 This reflects a higher prevalence compared to other series in the Caucasian population (10–15%). In the largest series of Australian patients with NSCLC, the authors also described the prevalence of other driver alterations such as KRAS (38.3%), BRAF (5.1%), or ERBB2 (1.7%) mutations.…”

Section: Lung Cancer In Oceaniamentioning

confidence: 99%

“…In the largest series of Australian patients with NSCLC, the authors also described the prevalence of other driver alterations such as KRAS (38.3%), BRAF (5.1%), or ERBB2 (1.7%) mutations. 165 Some studies have attempted to determine the differences in biomarkers prevalence among different ethnicities in northern Australia, 166 but due to the small sample size, no significant differences were found in the prevalence of EGFR or KRAS mutations. In the New Zealand population, in a cohort of 384 patients with NSCLC, 167 the overall prevalence of EGFR mutation was 22.5%, with a higher prevalence among the Asian population (51.8%), followed by Pacific Islanders (29%) and New Zealand Europeans (16.5%), while Māori had the lowest proportion (10.9%).…”

Section: Lung Cancer In Oceaniamentioning

confidence: 99%

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Geographic differences in lung cancer: focus on carcinogens, genetic predisposition, and molecular epidemiology

Laguna,

García-Pardo,

Alessi

et al. 2024

Ther Adv Med Oncol

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Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages. Hence, prevention and early diagnosis emerge as the most efficient strategies to enhance outcomes. In Western societies, tobacco consumption constitutes the primary risk factor for lung cancer, accounting for up to 90% of cases. In other geographic locations, different significant factors play a fundamental role in disease development, such as individual genetic predisposition, or exposure to other carcinogens such as radon gas, environmental pollution, occupational exposures, or specific infectious diseases. Comprehensive clinical and molecular characterization of lung cancer in recent decades has enabled us to distinguish different subtypes of lung cancer with distinct phenotypes, genotypes, immunogenicity, treatment responses, and survival rates. The ultimate goal is to prevent and individualize lung cancer management in each community and improve patient outcomes.

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“…6 Nevertheless, this contrasts to the more recent report from a single Australian laboratory experience where 28% of 1833 lung cancers harboured EGFR mutations. 7 The reason for this large discrepancy could be several fold: (1) the single laboratory might not reflect the broader Australian population as with this series, which was matched to the VCR; (2) the study used a next generation sequence (NGS) based approach which might be argued as more sensitive and thus pick up mutations not identified using technologies used in this study; (3) the NGS test used might have a specificity issue with generation of false positives; 8 and (4) differences in the Australian population have occurred since the closure of this program. The differences in these data are important to highlight as government health economic planning, test and drug reimbursement modelling of health costs for w12% difference in overall EGFR mutation rates would significantly increase costs of the government funding and interfere with health planning.…”

Section: Sirmentioning

confidence: 99%