Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant Kinases

Institute of Biostatistics, Fudan University, Shanghai, Shanghai Shi, China
Journal of Clinical Oncology (Impact Factor: 17.88). 10/2010; 28(30):4616-20. DOI: 10.1200/JCO.2010.29.6038
Source: PubMed

ABSTRACT To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations.
In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1.
Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations.
To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.


Available from: Hongbin Ji, Mar 23, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lung cancer is both the most common diagnosed cancer and the leading cause of cancer related deaths in China. During the past three decades, the incidence and mortality of lung cancer in China are increasing rapidly. According to data from National Central Cancer Registry (NCCR) in 2010, the crude incidence of lung cancer in China was 46.08 per 100,000 population (61.86 per 100,000 men and 29.54 per 100,000 women), with an estimated over 600,000 new diagnosed lung cancer patients (416,333 males and 189,613 females). Meanwhile, the crude mortality of lung cancer in China was 37.00 per 100,000 population (50.04 per 100,000 men and 23.33 per 100,000 women). Consistent with the change in developed countries, adenocarcinoma has become the most predominant histological subtype of lung cancer in China. For the majority advanced non-small-cell lung cancer (NSCLC) patients, especially patients with adenocarcinoma, targeted therapy became increasing important in the treatment. Chinese researcher have done a lot work in terms of lung cancer molecular epidemiology, therefore, in this review, we further summarized the epidemiology of driver genes in NSCLC, hoping to help clinicians to better screen certain driver genes in China for treatment decisions.
    10/2014; 3(5):270-9. DOI:10.3978/j.issn.2218-6751.2014.09.01
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of stereotactic ablative radiotherapy (SABR) as primary treatment for early stage non-small-cell lung cancer, or for ablation of metastases, has increased rapidly in the past decade. With local recurrence rates reported at approximately 10%, and a patient population that is becoming increasingly fit and amenable to salvage treatment, appropriate multidisciplinary follow-up care is critical. Appropriate follow-up will allow for detection and management of radiation-related toxicity, early detection of recurrent disease and differentiation of recurrence from radiation-induced lung injury. This narrative review summarizes issues surrounding follow-up of patients treated with SABR in the context of a multidisciplinary perspective. We summarize treatment-related toxicities including radiation pneumonitis, chest wall pain, rib fracture, and fatal toxicity, and highlight the challenges of early and accurate detection of local recurrence, while avoiding unnecessary biopsy or treatment of benign radiation-induced fibrotic lung damage. Follow-up recommendations based on the current evidence and available guidelines are summarized. Imaging follow-up recommendations include serial computed tomography (CT) imaging at 3-6 months posttreatment for the initial year, then every 6-12 months for an additional 3 years, and annually thereafter. With suspicion of progressive disease, recommendations include a multidisciplinary team discussion, the use of high-risk CT features for accurate detection of local recurrence, and positron emission tomography/CT SUVmax cutoffs to prompt further investigation. Biopsy and/or surgical or nonsurgical salvage therapy can be considered if safe and when investigations are nonreassuring. The appropriate follow-up of patients after SABR requires collaborative input from nearly all members of the thoracic multidisciplinary team, and evidence is available to guide treatment decisions. Further research is required to develop better predictors of toxicity and recurrence.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2015; 10(3):412-9. DOI:10.1097/JTO.0000000000000435 · 5.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Point mutation of the BRAF gene is a genetic event that occurs in a subset of lung adenocarcinoma cases. For example, BRAF V600E is a driver mutation that can be effectively targeted using selective BRAF and/or MEK inhibitors. The present study hypothesized that an increase in BRAF copy number may be correlated with certain clinicopathological features of lung adenocarcinoma in Japanese patients. The BRAF gene copy number was analyzed using quantitative polymerase chain reaction amplifications in 29 surgically treated lung adenocarcinoma cases without EGFR or Kras mutations from Nagoya City University Hospital (Nagoya, Japan). Seven BRAF-mutant cases were included. Increased BRAF gene copy number was identified in three lung adenocarcinoma patients (10.3%), all of which exhibited the V600E mutation. Using fluorescence in situ hybridization with BRAF-specific and chromosome 7 centromeric probes, increased copy number status was associated with gene amplification or gain of chromosome 7. Although increased BRAF copy number was correlated with BRAF V600E mutations, numerical changes in BRAF copy number were rare and mild in lung adenocarcinoma, resulting in no significant difference in pathological tumor status or tumor stage.
    Oncology letters 02/2015; 9(2):709-712. DOI:10.3892/ol.2014.2719 · 0.99 Impact Factor