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https://www.readbyqxmd.com/read/28097440/prevalence-of-nras-pten-and-akt1-gene-mutations-in-the-central-nervous-system-metastases-of-non-small-cell-lung-cancer
#1
Marcin Nicoś, Paweł Krawczyk, Bożena Jarosz, Marek Sawicki, Tomasz Trojanowski, Janusz Milanowski
Somatic mutations in NRAS, PTEN and AKT1 genes are rarely (~1%) reported in primary NSCLC, but their role in carcinogenesis have been proven. Therefore, we assessed the frequency of them in 145 FFPE tissue samples from CNS metastases of NSCLC using the real-time PCR technique. We identified four (two NRAS and single AKT1 and PTEN) mutations in CNS metastases of NSCLC. All mutations were observed in current male smokers (4% out of the male group; 4/100 and 4.25% out of smokers; 4/94). Three mutations have been detected in patients with SqCC (10...
January 17, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28095174/medical-oncologists-experiences-in-using-genomic-testing-for-lung-and-colorectal-cancer-care
#2
Stacy W Gray, Benjamin Kim, Lynette Sholl, Angel Cronin, Aparna R Parikh, Carrie N Klabunde, Katherine L Kahn, David A Haggstrom, Nancy L Keating
PURPOSE: Genomic testing improves outcomes for many at-risk individuals and patients with cancer; however, little is known about how genomic testing for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) is used in clinical practice. PATIENTS AND METHODS: In 2012 to 2013, we surveyed medical oncologists who care for patients in diverse practice and health care settings across the United States about their use of guideline- and non-guideline-endorsed genetic tests...
January 17, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28092948/oral-cell-dna-adducts-as-potential-biomarkers-for-lung-cancer-susceptibility-in-cigarette-smokers
#3
Stephen S Hecht
This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#4
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28065467/lung-adenocarcinoma-with-muc4-expression-is-associated-with-smoking-status-her2-protein-expression-and-poor-prognosis-clinicopathologic-analysis-of-338-cases
#5
Mariyo Rokutan-Kurata, Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Mizuki Koyama, Shohei Shigeto, Masakazu Fujimoto, Meng Zhang, Satoshi Morita, Hiroshi Date, Hironori Haga
BACKGROUND: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. PATIENTS AND METHODS: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28063177/comparable-clinical-outcomes-in-patients-with-her2-mutant-and-egfr-mutant-lung-adenocarcinomas
#6
Chien-Hung Gow, Hou-Tai Chang, Chor-Kuan Lim, Chao-Yu Liu, Jin-Shing Chen, Jin-Yuan Shih
HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients...
January 7, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28061772/use-of-liquid-biopsies-to-monitor-disease-progression-in-a-sarcoma-patient-a-case-report
#7
Heidi M Namløs, Olga Zaikova, Bodil Bjerkehagen, Daniel Vodák, Eivind Hovig, Ola Myklebost, Kjetil Boye, Leonardo A Meza-Zepeda
BACKGROUND: Many patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient. CASE PRESENTATION: A 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28048737/mo-de-207b-01-jack-fowler-junior-investigator-competition-winner-between-somatic-mutations-and-pet-based-radiomic-features-in-non-small-cell-lung-cancer
#8
S Yip, J Kim, T Coroller, E Rios Velazquez, C Parmar, R Mak, H Aerts
PURPOSE: Although PET-based radiomic features have been proposed to quantify tumor heterogeneity and shown promise in outcome prediction, little is known about their relationship with tumor genetics. This study assessed the association of [(18) F]fluorodeoxyglucose (FDG)-PET-based radiomic features with non-small cell lung cancer (NSCLC) mutations. METHODS: 348 NSCLC patients underwent FDG-PET/CT scans before treatment and were tested for genetic mutations. 13% (44/348) and 28% (96/348) patients were found to harbor EGFR (EGFR+) and KRAS (KRAS+) mutations, respectively...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043144/association-of-egfr-and-kras-mutations-with-expression-of-p-akt-dr5-and-dcr1-in-non-small-cell-lung-cancer
#9
X D Zhao, H B Deng, C L Lu, Y X Bao, X Lu, L L Deng
The activation of AKT is one of the causes of resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combines with related receptors to trigger apoptosis or protect the cells against TRAIL apoptosis. This research focused on the association of EGFR and KRAS mutations with expression of AKT, p-AKT, DR5 and DcR1 in non-small cell lung cancer. 82 NSCLC patients were included in the study. xTAG liquichip techonolgy (xTAG-LCT) was applied to investigate the genetic mutation of EGFR and KRAS, Quantitative Real-time PCR was used to test the mRNA expression of AKT, DR5 and DcR1 and Western Blot was applied to test the protein expression of AKT, p-AKT, DR5, and DcR1...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#10
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28035073/microrna-expression-profiles-and-clinicopathological-implications-in-lung-adenocarcinoma-according-to-egfr-kras-and-alk-status
#11
Hyojin Kim, Jeong Mi Yang, Yan Jin, Sanghoon Jheon, Kwhanmien Kim, Choon Taek Lee, Jin-Haeng Chung, Jin Ho Paik
Lung adenocarcinoma has distinctive clinicopathological features that are related to specific genetic alterations, including EGFR and KRAS mutations and ALK rearrangement. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate many important biological processes and influence cancer phenotypes. This study retrospectively investigated microRNA expression profiles, and their clinicopathological implications, in lung adenocarcinoma according to genetic status (EGFR, KRAS, ALK, and triple negative)...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031175/adjuvant-folfox-cetuximab-in-full-ras-and-braf-wildtype-stage-iii-colon-cancer-patients
#12
J Taieb, R Balogoun, K Le Malicot, J Tabernero, E Mini, G Folprecht, J-L Van Laethem, J-F Emile, C Mulot, S Fratté, C-B Levaché, L Saban-Roche, J Thaler, L N Petersen, J Bridgewater, G Perkins, C Lepage, E Van Cutsem, A Zaanan, P Laurent-Puig
BACKGROUND: RAS mutations have been shown to confer resistance to anti-EGFR treatment. We analyzed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. METHODS: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumors harboring RAS & BRAF WT and RAS mutations...
December 28, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28024928/molecular-profiling-and-survival-of-completely-resected-primary-pulmonary-neuroendocrine-carcinoma
#13
Guangyuan Lou, Xinmin Yu, Zhengbo Song
BACKGROUND: Currently, molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are poorly elucidated. The present study was designed to evaluate genomic abnormalities and survival in patients with primary PNC. METHODS: Completely resected PNC samples were collected from Zhejiang Cancer Hospital during the period of 2008 to 2015. Nine driver genes, including 6 mutations (EGFR, KRAS, NRAS, PIK3CA, BRAF, and HER2) and 3 fusions (ALK, ROS1, and RET), were evaluated by reverse transcription-polymerase chain reaction (RT-PCR)...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28024701/a-comprehensive-analysis-of-clinical-outcomes-in-lung-cancer-patients-harboring-a-met-exon-14-skipping-mutation-compared-to-other-driver-mutations-in-an-east-asian-population
#14
Chien-Hung Gow, Min-Shu Hsieh, Shang-Gin Wu, Jin-Yuan Shih
INTRODUCTION: Recurrent somatic splice-site alterations at MET exon 14 (MET(Δ14)), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined. METHODS: A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancer patients, was performed in order to detect MET(Δ14) and five other major driver mutations, including those in the EGFR, KRAS, ALK, HER2, and ROS1 genes...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28018973/inactivation-of-abl-kinases-suppresses-non-small-cell-lung-cancer-metastasis
#15
Jing Jin Gu, Clay Rouse, Xia Xu, Jun Wang, Mark W Onaitis, Ann Marie Pendergast
Current therapies to treat non-small cell lung carcinoma (NSCLC) have proven ineffective owing to transient, variable, and incomplete responses. Here we show that ABL kinases, ABL1 and ABL2, promote metastasis of lung cancer cells harboring EGFR or KRAS mutations. Inactivation of ABL kinases suppresses NSCLC metastasis to brain and bone, and other organs. ABL kinases are required for expression of prometastasis genes. Notably, ABL1 and ABL2 depletion impairs extravasation of lung adenocarcinoma cells into the lung parenchyma...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28012356/radiogenomic-evaluation-of-lung-cancer-are-there-imaging-characteristics-associated-with-lung-adenocarcinomas-harboring-braf-mutations
#16
Darragh F Halpenny, Andrew Plodkowski, Gregory Riely, Junting Zheng, Anya Litvak, Chaya Moscowitz, Michelle S Ginsberg
INTRODUCTION: We studied computed tomography (CT) features associated with BRAF mutated lung cancer. MATERIALS AND METHODS: CT features of BRAF mutated lung cancers were compared to stage matched lesions without BRAF mutation. RESULTS: 47 (25%) patients with BRAF mutation and 141 (75%) without BRAF mutation were included. BRAF lesions were most frequently solid 37 (84%), spiculated 22 (50%), and peripheral 37 (84%). No feature of the primary tumor was significantly different between BRAF and non-BRAF groups...
November 30, 2016: Clinical Imaging
https://www.readbyqxmd.com/read/28007785/p38mapk-builds-a-hyaluronan-cancer-niche-to-drive-lung-tumorigenesis
#17
Anna Brichkina, Thomas Bertero, Hui Mun Loh, Nguyet Thi Minh Nguyen, Alexander Emelyanov, Sidwell Rigade, Marius Ilie, Paul Hofman, Cedric Gaggioli, Dmitry V Bulavin
Expansion of neoplastic lesions generates the initial signal that instigates the creation of a tumor niche. Nontransformed cell types within the microenvironment continuously coevolve with tumor cells to promote tumorigenesis. Here, we identify p38MAPK as a key component of human lung cancer, and specifically stromal interactomes, which provides an early, protumorigenic signal in the tissue microenvironment. We found that lung cancer growth depends on short-distance cues produced by the cancer niche in a p38-dependent manner...
December 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/28007627/clinical-outcome-of-alk-positive-non-small-cell-lung-cancer-nsclc-patients-with-de-novo-egfr-or-kras-co-mutations-receiving-tyrosine-kinase-inhibitors-tki
#18
Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Früh Martin
BACKGROUND: Non-small cell lung cancer (NSCLC) with de novo anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations co-occur very rarely. Outcomes with tyrosine kinase inhibitors (TKIs) in these patients (pts) are poorly understood. METHODS: Outcomes of pts with metastatic NSCLC de novo co- alterations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and sequencing (EGFR/KRAS) from six Swiss centres were analysed...
December 19, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27999749/growth-and-metastasis-of-lung-adenocarcinoma-is-potentiated-by-bmp4-mediated-immunosuppression
#19
Limo Chen, Xiaohui Yi, Sangeeta Goswami, Young-Ho Ahn, Jonathon D Roybal, Yongbin Yang, Lixia Diao, Di Peng, David Peng, Jared J Fradette, Jing Wang, Lauren A Byers, Jonathan M Kurie, Stephen E Ullrich, F Xiao-Feng Qin, Don L Gibbons
Cancer cells modulate the recruitment and function of inflammatory cells to create an immunosuppressive microenvironment that favors tumor growth and metastasis. However, the tumor-derived regulatory programs that promote intratumoral immunosuppression remain poorly defined. Here, we show in a Kras(LA1/+)p53(R172HΔg/+)-based mouse model that bone morphogenetic protein-4 (BMP4) augments the expression of the T cell co-inhibitory receptor ligand PD-L1 in the mesenchymal subset of lung cancer cells, leading to profound CD8(+) T cell-mediated immunosuppression, producing tumor growth and metastasis...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999344/egfr-and-kras-mutations-predict-the-incidence-and-outcome-of-brain-metastases-in-non-small-cell-lung-cancer
#20
Pascale Tomasini, Cindy Serdjebi, Nataliya Khobta, Philippe Metellus, L'Houcine Ouafik, Isabelle Nanni, Laurent Greillier, Anderson Loundou, Frederic Fina, Celine Mascaux, Fabrice Barlesi
BACKGROUND: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. METHODS: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients' outcome were assessed...
December 18, 2016: International Journal of Molecular Sciences
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