scholarly journals Impaired ligand‐dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer

2019 ◽  
Vol 110 (10) ◽  
pp. 3340-3349 ◽  
Author(s):  
Wenyu Miao ◽  
Katsuya Sakai ◽  
Hiroki Sato ◽  
Ryu Imamura ◽  
Nawaphat Jangphattananont ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Missense Mutation ◽  
Sema Domain

Secondary T790M mutation and novel G796A mutation in exon20 of EGFR gene in patients with non-small cell lung cancer who show resistance to gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7703-7703
Author(s):  
H. Uramoto ◽  
K. Sugio ◽  
T. Oyama ◽  
T. Iwata ◽  
T. Onizuka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Missense Mutation ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Egfr Gene

7703 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to a tyrosine kinase inhibitor (TKI). EGFR mutations occur predominantly in exon19 and/or exon21, namely, an in-frame deletion in exon19 or a missense mutation in exon21 (L858R), which have been found to be related to the sensitivity to TKI. However, most patients with such sensitive mutations in their tumor show progression during the TKI treatment. In such resistant tumors, a secondary threonine- to-methionine mutation at codon 790 (T790M) in exon20 has been reported to be related the resistance to either gefitinib or erlotinib. Methods: EGFR mutations in exons19–21 were examined by sequencing in 37 pretreatment tumors obtained from patients with NSCLC, who were treated by gefitinib. Of the 22 cases having sensitive EGFR mutations (19del or L858R), 15 showed CR/PR and 7 showed SD/PD. Of the 15 patients with CR/PR, 4 tumor samples (2 lung, 1 liver, and 1 pleural effusion) that became refractory to gefitinib, were obtained. In pretreatment tumor samples from 4 patients, an in-frame deletion of exon19 was observed in 3 tumors and a L858R mutation of exon21 was in 1 tumor. We next examined whether a secondary mutation occurred in a tumor with acquired resistance to gefitinib in 4 patients by the sequencing of exons 19–21, with informed consent. Results: Three of 4 tumor samples had a secondary T790M mutation, which was not detected in the pretreatment tumor samples. These 3 samples also had an in-frame deletion in exon19. There were no other novel secondary mutations in exons 19,20,21. In 7 cases showing resistance to gefitinib (SD/PD) in spite of the existence of sensitive mutations, 1 tumor demonstrated the co-existence of a missense mutation (G796A) in exon20. In vitro, a stable clone of cells bearing the G796A mutation was approximately 50,000-fold less sensitive to gefitinib in comparison to the cells carrying exon19 deletion. Conclusions: The T790M mutation is common in patients with acquired resistance to gefitinb. Our results suggest that screening tumor samples for a range of EGFR mutations may therefore improve our ability to identify the patients most likely to benefit from treatment with TKI. No significant financial relationships to disclose.

R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability

2015 ◽  
Vol 33 (20) ◽  
pp. 2303-2310 ◽  
Author(s):  
Hsuan-Yu Chen ◽  
Sung-Liang Yu ◽  
Bing-Ching Ho ◽  
Kang-Yi Su ◽  
Yi-Chiung Hsu ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Missense Mutation ◽  
Low Dose ◽  
Risk Allele ◽  
Allele Carrier ◽  
Risk Alleles ◽  
Computed Tomography Scans ◽  
Low Dose Computed Tomography

Purpose Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential. Patients and Methods Whole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities. Results YAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells. Conclusion These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

scholarly journals The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells

Oncogenesis ◽  
2018 ◽  
Vol 7 (12) ◽  
Author(s):  
Cheng-Ying Shen ◽  
Ya-Chu Chang ◽  
Li-Han Chen ◽  
Wen-Chun Lin ◽  
Yung-Hua Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Apoptotic Signaling ◽  
Sema Domain

A prospective phase II study of gefitinib in non-small cell cancer patients with epidermal growth factor receptor gene (EGFR) mutations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18081-18081 ◽  
Author(s):  
K. Sugio ◽  
H. Uramoto ◽  
T. Oyama ◽  
T. Onizuka ◽  
Y. Ichiki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Informed Consent ◽  
Survival Time ◽  
Missense Mutation ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Screening Method ◽  
Small Cell ◽  
Egfr Mutations ◽  
Exon 19

18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to gefitinib, a tyrosine kinase inhibitor that targets EGFR, especially in patients with adenocarcinoma, females, and/or never/light smokers. In our retrospective study, cases with EGFR mutations (exon19del or L858R) showed a high sensitivity to gefitinib, and the patients with sensitive EGFR mutations also tended to have a more favorable prognosis than those with wild-type after gefitinib treatment (Uramoto, et al. Lung Cancer 2006;51:71). In the present study, we prospectively assessed the efficacy of gefitinib and the survival benefit for patients with EGFR mutations. Methods: Patients with either recurrent disease after undergoing surgery or advanced disease (IIIB or IV) of NSCLC which demonstrated EGFR mutations were eligible for this study. EGFR mutations in exons 19–21 were examined by our previously described screening method (Sugio, et al. Br J Cancer 2006;94:896) and confirmed by direct sequencing after informed consent was obtained from all patients. The patients with EGFR mutations were enrolled in this study after obtaining informed consent a second time, and they were thereafter treated with gefitinib. Results: Between 2005 and 2006, 16 patients (10 males/6 females, all adenocarcinoma) who had EGFR mutations were enrolled onto this study. Six pts had a deletion in exon 19, 8 pts had a missense mutation in exon 21 (L858R), 1 pt had both an exon 19 del and L858R, and 1 pts had an exon19 del and missense mutation in exon 20 (G796A). The overall response rate was 50%, and the disease control rate was 88%. In patients with exon19 del and L858R, the response rates were 83% and 25%, respectively. A case with a deletion in exon19 and a missense mutation in exon20 (G796A) showed resistance to gefitinib. The median progression-free survival time was 8.8 months, and the median survival time was 15.4 months. No life-threatening toxicity was observed. Conclusions: EGFR mutations in exons 19 or 21 are therefore considered to a good predictor of the efficacy of gefitinib, and the treatment with gefitinib was also found to achieve a prolonged survival. No significant financial relationships to disclose.

Comment: predictability of survival in the individual patient with lung cancer

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1036-1037 ◽  
Author(s):  
P. Rubin
Keyword(s):  
Lung Cancer ◽  
The Individual

The question of irradiation therapy in lung cancer

JAMA ◽  
1966 ◽  
Vol 195 (6) ◽  
pp. 471-475 ◽  
Author(s):  
M. J. Krant
Keyword(s):  
Lung Cancer ◽  
Irradiation Therapy

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

Use of Tumor Markers in Lung Cancer

1994 ◽  
Vol 8 (3) ◽  
pp. 507-532 ◽  
Author(s):  
Gary M. Strauss ◽  
Arthur T. Skarin
Keyword(s):  
Lung Cancer ◽  
Tumor Markers

Small cell lung cancer

2001 ◽  
Vol 37 ◽  
pp. 61-63
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer

2001 ◽  
Vol 37 ◽  
pp. 47-61
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung
Sign in / Sign up

Export Citation Format

Share Document