Supplementary Table 19 from Activating Point Mutations in the <i>MET</i> Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors
Federica PecciSeshiru NakazawaBiagio RicciutiGuilherme HaradaJessica LeeJoao V. AlessiAdriana BarrichelloVictor R. VazGiuseppe LambertiAlessandro Di FedericoMalini GandhiDimitris GazgalisWilliam W. FengJie JiangSimon BaldacciMarie-Anaïs LocquetFelix H. GottliebMonica F. ChenElinton LeeDanielle HaradonAnna SmokovichEmma VolignyTom NguyenVikas K. GoelZachary ZimmermanSumandeep AtwalXinan WangMagda BahcallRebecca S. HeistSumaiya IqbalNishant GandhiAndrew ElliottAri M. VanderwaldeC. PatrickBalázs HalmosStephen V. LiuJianwei CheAlexa B. SchrockAlexander DrilonPasi A. JänneMark M. Awad
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<p>Detailed clinicopathologic and genomic characteristics related to renal cell cancer cases in cohort #1.</p>Keywords:
Protein kinase domain
Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer.
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Abstract Leading investigators generally agree that a significant part of the observed increase in lung cancer mortality represents a real increase in the rate at which lung cancer is developing in the population. This increase cannot reasonably be attributed to genetic change in the human population and therefore must be due to environmental factors. Available evidence linking tobacco smoking to lung cancer is fairly extensive and impressive: (1) The increase in lung cancer mortality has been generally parallel to an increase in cigarette consumption; (2) In each of 14 case history studies there was a smaller percentage of non-smokers and a higher percentage of heavy smokers among lung cancer patients than among comparable controls; (3) Preliminary results of two population studies indicate higher mortality from lung cancer among smokers than among non-smokers and a still higher mortality among heavy smokers; and (4) At least one team of investigators has produced skin cancer in animals with condensates of tobacco smoke. There is disagreement whether the evidence at hand warrants a conclusion that smoking and lung cancer are causally related. The relative importance of smoking, air pollution, and occupational exposure to cancerigenic materials remains to be established.
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Objective To analyze the mutations of ABL tyrosine kinase in chronic myeloid leukemia(CML) patients who were resistant to imatinib.Methods A total of 56 bone marrow samples from the patients resistant to imatinib were analyzed by nested polymerase chain reaction to amplify ABL kinase domain,followed by direct sequencing and sequence homologous analysis.Results Among the 56 samples analyzed,ABL domain mutations were found in 17 samples which included 14 point mutations and 3 insertion mutations.The point mutations presented with 8 types of nucleotide changes,namely T315I,N358D,F359V,T389A,P441L,E450K,S410G and F486S.All the 3 insertion mutations were c.1423-1424ins 35bp(p.C475YfsX11).Among the 17 mutations,the number of cases in chronic phase(CP),accelerated phase(AP) and blast phase(BP) was 12,4 and 1,respectively.The incidences of mutation in both AP and BP of CML were higher than that in CP.Conclusion ABL kinase point mutation may be an important mechanism for imatinib resistance.The detection of ABL kinase point mutations should be helpful to estimate the prognosis and adjust the therapeutic strategy.
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Lung cancer has been viewed as the most common malignant cancer with high incidence, mortality and poor survival all over the world. A lot of investigations indicated there are significant gender-associated differences in lung cancer in several characteristics such as epidemiology, pathology, clinical outcome and prognosis. The insight into these differences may help to clarify the gender-associated characteristics of lung cancer, and to drawn out new approach for treatment and prevent of lung cancer depending on gender-associated characteristics. Furthermore, study on mechanism of gender-associated characteristics may even help to illuminate the pathogenesis of lung cancer.
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Objective:To investigate the expression level of adrenomedulin(ADM)in lung cancer patients,the relationship be- tween ADM and the pathological type and stage of lung cancer.Methods:We determined the content of ADM in plasma of 20 healthy adults,24 non-lung cancer patients and 61 lung cancer patients by use of radioimmunoassay.Results:The content of ADM in the plasma of healthy control group was 30.25±8.12 pg/L,lung cancer group was 40.17±19.23 pg/L,there was significant difference between them(P＜0.05) ;The content of ADM in the plasma of non-lung cancer group was 27.94±6.75 pg/L,compared with lung cancer group,there was significant difference(P＜0.01 );Small cell lung cancer group compared with non-small cell lung cancer group,the content of ADM in plasma had no significant difference(P＞0.{)5) ;Ⅰ-Ⅲstage of lung cancer group compared withⅣstage group,the content of ADM in plasma had significant difference(P＜0.05).Conclusion: The expression level of ADM in plasma of lung cancer increased,the expression level of ADM was correlated with the stage of lung cancer and distant metastasis,No correlation was found between ADM level and the pathological type of lung cancer. Therefore,detecting ADM in plasma had great value in lung cancer diagnosis and staging,and provided a new way to lung cancer diagnosis.
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This study was purposed to evaluate ABL tyrosine kinase point mutations in imatinib-treated chronic myeloid leukemia (CML) patients and their clinical significance. 51 bone marrow samples from 28 imatinib-resistant patients and 10 newly diagnosed CML patients were collected. ABL kinase domain of bcr-abl allele was amplified by nested reverse transcription-polymerase chain reaction, followed by purifying, directly sequencing and sequence homology analysis of amplified products in order to determine the existence and type of point mutation. The results showed that the point mutations were found in 12 of 38 patients, and all the 12 ones progressed to advanced disease or death. 2 patients showed Met351Thr mutation, 7 patients showed Glu252His, 2 patients showed Glu279Lys, the other types were Glu255Val and Glu355Gly, each of which was tested in one patient. The incidence of the point mutation was 17.6%, 45.5% and 44.4% in chronic, accelerated and blast phase respectively. The incidences of point mutation in hematologically and genetically resistant patients were 50% (5/10) and 44.4% (8/18), and the 95% confidence interval (CI) was 12.3% - 87.7% and 19% - 69.9% respectively. It is concluded that ABL kinase point mutation is an important mechanism of imatinib resistance, monitoring the ABL kinase domain point mutation is helpful to estimating the prognosis and adjusting the therapeutic strategy.
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ABL
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