+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations



Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations



Journal of Thoracic Oncology 9(4): 456-463



Hereditary lung cancer syndromes are rare, and T790M germline mutations of the epidermal growth factor receptor (EGFR) gene predispose to the development of lung cancer. The goal of this study was to determine the clinical features and smoking status of lung cancer cases and unaffected family members with this germline mutation and to estimate its incidence and penetrance. We studied a family with germline T790M mutations over five generations (14 individuals) and combined our observations with data obtained from a literature search (15 individuals). T790M germline mutations occurred in approximately 1% of non-small-cell lung cancer cases and in less than one in 7500 subjects without lung cancer. Both sporadic and germline T790M mutations were predominantly adenocarcinomas, favored female gender, and were occasionally multifocal. Of lung cancer tumors arising in T790M germline mutation carriers, 73% contained a second activating EGFR gene mutation. Inheritance was dominant. The odds ratio that T790M germline carriers who are smokers will develop lung cancer compared with never smoker carriers was 0.31 (p = 6.0E-05). There was an overrepresentation of never smokers with lung cancer with this mutation compared with the general lung cancer population (p = 7.4E-06). Germline T790M mutations result in a unique hereditary lung cancer syndrome that targets never smokers, with a preliminary estimate of 31% risk for lung cancer in never smoker carriers, and this risk may be lower for heavy smokers. The resultant cancers share several features and differences with lung cancers containing sporadic EGFR mutations.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053522726

Download citation: RISBibTeXText

PMID: 24736066

DOI: 10.1097/JTO.0000000000000130


Related references

A patient with metastatic lung adenocarcinoma harboring concurrent EGFR L858R, EGFR germline T790M, and PIK3CA mutations: the challenge of interpreting results of comprehensive mutational testing in lung cancer. Journal of the National Comprehensive Cancer Network 12(1): 6-11; Quiz 11, 2014

Screening for germline EGFR T790M mutations through lung cancer genotyping. Journal of Thoracic Oncology 7(6): 1049-1052, 2012

EGFR -Mutant Non-Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline EGFR T790M Testing. Journal of the National Comprehensive Cancer Network 15(10): 1188-1192, 2018

MA 15.08 Safety and Efficacy of Osimertinib in Treating an EGFR-Mutant Lung Cancer Patient with a Germline EGFR T790M Mutation. Journal of Thoracic Oncology 12(11): S1863-S1864, 2017

Germline Mutation of T790M and Dual/Multiple EGFR Mutations in Patients With Lung Adenocarcinoma. Clinical Lung Cancer 17(2): E5-11, 2016

EGFR C797S, EGFR T790M and EGFR sensitizing mutations in non-small cell lung cancer revealed by six-color crystal digital PCR. Oncotarget 9(100): 37393-37406, 2019

The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR-T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations. Bmc Cancer 18(1): 1241-1241, 2018

Case report of three EGFR TKI naïve lung adenocarcinoma containing double EGFR mutations (L858R/T790M or Exon 19 Deletion/T790M); Comparing genetic information and histology. Pathology, Research and Practice 214(8): 1224-1230, 2018

Discrimination of Germline EGFR T790M Mutations in Plasma Cell-Free DNA Allows Study of Prevalence Across 31,414 Cancer Patients. Clinical Cancer Research 23(23): 7351-7359, 2017

Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discovery 4(9): 1036-1045, 2016

T790M-Selective EGFR-TKI Combined with Dasatinib as an Optimal Strategy for Overcoming EGFR-TKI Resistance in T790M-Positive Non-Small Cell Lung Cancer. Molecular Cancer Therapeutics 16(11): 2563-2571, 2017

Comparison of detection methods of EGFR T790M mutations using plasma, serum, and tumor tissue in EGFR-TKI-resistant non-small cell lung cancer. Oncotargets and Therapy 11: 3335-3343, 2018

Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clinical Cancer Research 17(5): 1160-1168, 2011

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs. Oncotargets and Therapy 10: 2267-2279, 2017

Most T790M mutations are present on the same EGFR allele as activating mutations in patients with non-small cell lung cancer. Lung Cancer 108: 75-82, 2018