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https://www.readbyqxmd.com/read/28921573/contralateral-breast-cancers-independent-cancers-or-metastases
#1
Colin B Begg, Irina Ostrovnaya, Felipe C Geyer, Anastasios D Papanastasiou, Charlotte Ky Ng, Rita Sakr, Jonine L Bernstein, Kathleen A Burke, Tari A King, Salvatore Piscuoglio, Audrey Mauguen, Irene Orlow, Britta Weigelt, Venkatraman E Seshan, Monica Morrow, Jorge S Reis-Filho
A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28918548/tumor-and-serum-dna-methylation-in-women-receiving-preoperative-chemotherapy-with-or-without-vorinostat-in-tbcrc008
#2
Roisin M Connolly, Mary Jo Fackler, Zhe Zhang, Xian C Zhou, Matthew P Goetz, Judy C Boughey, Bridget Walsh, John T Carpenter, Anna Maria Storniolo, Stanley P Watkins, Edward W Gabrielson, Vered Stearns, Saraswati Sukumar
BACKGROUND: Methylated gene markers have shown promise in predicting breast cancer outcomes and treatment response. We evaluated whether baseline and changes in tissue and serum methylation levels would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer undergoing preoperative chemotherapy. METHODS: The TBCRC008 trial investigated pCR following 12 weeks of preoperative carboplatin and albumin-bound paclitaxel + vorinostat/placebo (n = 62)...
September 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28914263/coexistent-genetic-alterations-involving-alk-ret-ros1-or-met-in-15-cases-of-lung-adenocarcinoma
#3
Zhenya Tang, Jianjun Zhang, Xinyan Lu, Wei Wang, Hui Chen, Melissa K Robinson, Joanne Cheng, Guilin Tang, L Jeffrey Medeiros
In lung cancer, targetable activating alterations in cancer genes, such as EGFR, ALK, RET, ROS1 and MET, are usually mutually exclusive. Rare lung cancer cases with coexistent alterations of EGFR and ALK or EGFR mutations with RET or ROS1 rearrangements have been reported. In this study, we report 15 patients (3 men and 12 women; 14 Caucasians and 1 African American) with ages ranging from 43 to 81 years (median 60 years) with lung adenocarcinoma in which coexistent alterations of two cancer-associated genes, including ALK, ROS1, or RET rearrangement or MET amplification were present...
September 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#4
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28911263/potential-role-of-oct4-in-leukemogenesis
#5
Tiphanie Picot, Sanae Kesr, Yuenv Wu, Carmen Aanei, Pascale Flandrin-Gresta, Sylvie Tondeur, Emmanuelle Tavernier, Eric Wattel, Denis Guyotat, Lydia Campos
Embryonic stem cells typically show properties of long term self-renewal and lack of differentiation. When appropriately stimulated, they are able to differentiate into all cell lineages, and lose their self-renewal characteristics. These properties are controlled by a series of genes encoding several transcription factors including OCT4, the product of POU5F1 gene. OCT4 is expressed in germ-cell tumors, but also aberrantly in cancers developing in differentiated tissues. In a previous study, we observed a high expression of OCT4 in acute myeloid cell lines and primary cells, regardless of the Acute Myeloid Leukemia subtype...
September 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28911072/oncologist-use-and-perception-of-large-panel-next-generation-tumor-sequencing
#6
A M Schram, D Reales, J Galle, R Cambria, R Durany, D Feldman, E Sherman, J Rosenberg, G D'Andrea, S Baxi, Y Janjigian, W Tap, M Dickler, J Baselga, B S Taylor, D Chakravarty, J Gao, N Schultz, D B Solit, M F Berger, D M Hyman
Background: Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making. Patients and methods: All physicians who consented patients to MSK-IMPACT, a next-generation hybridization capture assay, in tumor types where molecular profiling is not routinely performed were asked to complete a questionnaire for each patient...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28904059/gene-methylation-biomarkers-in-sputum-and-plasma-as-predictors-for-lung-cancer-recurrence
#7
Steven A Belinsky, Shuguang Leng, Guodong Wu, Cynthia L Thomas, Maria A Picchi, Sandra J Lee, Seena Aisner, Suresh Ramalingam, Fadlo R Khuri, Daniel D Karp
Detection of methylated genes in exfoliated cells from the lungs of smokers provides an assessment of the extent of field cancerization, is a validated biomarker for predicting lung cancer, and provides some discrimination when interrogated in blood. The potential utility of this 8-gene methylation panel for predicting tumor recurrence has not been assessed. The Eastern Cooperative Oncology Group initiated a prevention trial (ECOG-ACRIN5597) that enrolled resected Stage I non-small cell lung cancer patients who were randomized 2:1 to receive selenized yeast versus placebo for four years...
September 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#8
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893223/brca2-carriers-with-male-breast-cancer-show-elevated-tumour-methylation
#9
Siddhartha Deb, Kylie L Gorringe, Jia-Min B Pang, David J Byrne, Elena A Takano, kConFab Investigators, Alexander Dobrovic, Stephen B Fox
BACKGROUND: Male breast cancer (MBC) represents a poorly characterised group of tumours, the management of which is largely based on practices established for female breast cancer. However, recent studies demonstrate biological and molecular differences likely to impact on tumour behaviour and therefore patient outcome. The aim of this study was to investigate methylation of a panel of commonly methylated breast cancer genes in familial MBCs. METHODS: 60 tumours from 3 BRCA1 and 25 BRCA2 male mutation carriers and 32 males from BRCAX families were assessed for promoter methylation by methylation-sensitive high resolution melting in a panel of 10 genes (RASSF1A, TWIST1, APC, WIF1, MAL, RARβ, CDH1, RUNX3, FOXC1 and GSTP1)...
September 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28892047/a-system-for-detecting-high-impact-low-frequency-mutations-in-primary-tumors-and-metastases
#10
M Anjanappa, Y Hao, E R Simpson, P Bhat-Nakshatri, J B Nelson, S A Tersey, R G Mirmira, A A Cohen-Gadol, M R Saadatzadeh, L Li, F Fang, K P Nephew, K D Miller, Y Liu, H Nakshatri
Tumor complexity and intratumor heterogeneity contribute to subclonal diversity. Despite advances in next-generation sequencing (NGS) and bioinformatics, detecting rare mutations in primary tumors and metastases contributing to subclonal diversity is a challenge for precision genomics. Here, in order to identify rare mutations, we adapted a recently described epithelial reprograming assay for short-term propagation of epithelial cells from primary and metastatic tumors. Using this approach, we expanded minor clones and obtained epithelial cell-specific DNA/RNA for quantitative NGS analysis...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28891048/identifying-actionable-variants-using-next-generation-sequencing-in-patients-with-a-historical-diagnosis-of-undifferentiated-pleomorphic-sarcoma
#11
Jeremy Lewin, Swati Garg, Beatrice Y Lau, Brendan C Dickson, Frank Traub, Nalan Gokgoz, Anthony M Griffin, Peter C Ferguson, Irene L Andrulis, Hao-Wen Sim, Suzanne Kamel-Reid, Tracy L Stockley, Lillian Siu, Jay S Wunder, Albiruni Ra Razak
There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re-evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons)...
September 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28890089/-tumour-sequencing-evolutions-and-revolutions
#12
N Piton, A Lamy, J-C Sabourin
For some years now, we have entered the genomic age of tumour genotyping from a medical point of view. Technological breakthroughs in both biology and information science now allow a genomic analysis of cancers in everyday medical practice with, in some case, a major impact on patient care not only for the choice of therapy (i.e. EGFR mutations in lung adenocarcinoma), but also for diagnosis and monitoring of the disease. Tumour genotyping is performed from formalin-fixed paraffin-embedded tissues used for diagnosis of cancer...
September 7, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28889351/multidimensional-phenotyping-of-breast-cancer-cell-lines-to-guide-preclinical-research
#13
Jodi M Saunus, Chanel E Smart, Jamie R Kutasovic, Rebecca L Johnston, Priyakshi Kalita-de Croft, Mariska Miranda, Esdy N Rozali, Ana Cristina Vargas, Lynne E Reid, Eva Lorsy, Sibylle Cocciardi, Tatjana Seidens, Amy E McCart Reed, Andrew J Dalley, Leesa F Wockner, Julie Johnson, Debina Sarkar, Marjan E Askarian-Amiri, Peter T Simpson, Kum Kum Khanna, Georgia Chenevix-Trench, Fares Al-Ejeh, Sunil R Lakhani
PURPOSE: Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish. METHODS: We performed multidimensional profiling of 36 widely used breast cancer cell lines that were cultured under standardised conditions...
September 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28888541/frequency-of-mutations-in-a-large-series-of-clinically-ascertained-ovarian-cancer-cases-tested-on-multi-gene-panels-compared-to-reference-controls
#14
Jenna Lilyquist, Holly LaDuca, Eric Polley, Brigette Tippin Davis, Hermela Shimelis, Chunling Hu, Steven N Hart, Jill S Dolinsky, Fergus J Couch, David E Goldgar
OBJECTIVES: Given the lack of adequate screening modalities, knowledge of ovarian cancer risks for carriers of pathogenic alterations in predisposition genes is important for decisions about risk-reduction by salpingo-oophorectomy. We sought to determine which genes assayed on multi-gene panels are associated with ovarian cancer, the magnitude of the associations, and for which clinically meaningful associations could be ruled out. METHODS: 7768 adult ovarian cancer cases of European ancestry referred to a single clinical testing laboratory underwent multi-gene panel testing for detection of pathogenic alterations in known or suspected ovarian cancer susceptibility genes...
September 7, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28884749/comprehensive-clinical-and-molecular-analyses-of-neuroendocrine-carcinomas-of-the-breast
#15
Marion Lavigne, Emmanuelle Menet, Jean-Christophe Tille, Marick Lae, Laetitia Fuhrmann, Claire Bonneau, Gabrielle Deniziaut, Samia Melaabi, Charlotte C K Ng, Caterina Marchiò, Roman Rouzier, Ivan Bièche, Anne Vincent-Salomon
Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial in the literature. The 2012 WHO classification of breast cancer categorizes neuroendocrine carcinomas into three morphologically distinct subtypes: well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. We aimed to gain insight into the clinical, morphologic, phenotypic, and molecular features of 47 neuroendocrine breast carcinomas...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28884193/neurotrophin-trk-receptors-new-targets-for-cancer-therapy
#16
Jacopo Meldolesi
In the last few years, exciting reports have emerged regarding the role of the two types of neurotrophin receptors, p75(NTR) and Trks, not only in neurons, where they were discovered, but also in non-neural cells and, especially, in numerous cancers, including breast, lung, colon-rectum, pancreas, prostate, glioblastoma, neuroblastoma, myeloma, and lymphoid tumors. Traditionally, p75(NTR), activated by all neurotrophins and their precursors, is an inhibitor. In various cancers, however, activated p75(NTR) induces variable effects, from inhibition to stimulation of cell proliferation, dependent on their direct or coordinate/indirect mechanism(s) of action...
September 8, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28881809/jagged-2-jag2-enhances-tumorigenicity-and-chemoresistance-of-colorectal-cancer-cells
#17
Vivek Vaish, Joohwee Kim, Minsub Shim
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Recent studies have stated that NOTCH signaling plays an important role in the development and progression of CRC. However, the role of Jagged-2 (JAG2), one of the NOTCH ligands, has not been delineated in colorectal tumorigenesis and drug resistance. In the present study, we have examined the impact of targeting JAG2 on CRC cells. Among all the members of NOTCH ligands, only the expression of JAG2 was found up-regulated in the intestinal tumors of Apc (Min) /+ mice as compared to the nearby normal mucosa...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881717/5-aza-2-deoxycytidine-dac-treatment-downregulates-the-hpv-e6-and-e7-oncogene-expression-and-blocks-neoplastic-growth-of-hpv-associated-cancer-cells
#18
Maximilian Stich, Lennard Ganss, Jens Puschhof, Elena-Sophie Prigge, Miriam Reuschenbach, Ana Guiterrez, Svetlana Vinokurova, Magnus von Knebel Doeberitz
High-risk human papillomaviruses (hr HPVs) may cause various human cancers and associated premalignant lesions. Transformation of the host cells is triggered by overexpression of the viral oncogenes E6 and E7 that deregulate the cell cycle and induce chromosomal instability. This process is accompanied by hypermethylation of distinct CpG sites resulting in silencing of tumor suppressor genes, inhibition of the viral E2 mediated control of E6 and E7 transcription as well as deregulated expression of host cell microRNAs...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881587/mgmt-and-calca-promoter-methylation-are-associated-with-poor-prognosis-in-testicular-germ-cell-tumor-patients
#19
Camila Maria da Silva Martinelli, André van Helvoort Lengert, Flavio Mavignier Cárcano, Eduardo Caetano Albino Silva, Mariana Brait, Luiz Fernando Lopes, Daniel Onofre Vidal
Testicular germ cell tumors (TGCT) represent the second main cause of cancer-related death in young men. Despite high cure rates, refractory disease results in poor prognosis. Epigenetic reprogramming occurs during the development of seminomas and non-seminomas. Understanding the molecular and genetic basis of these tumors would represent an important advance in the search for new TGCT molecular markers. Hence the frequency of methylation of a gene panel (VGF, MGMT, ADAMTS1, CALCA, HOXA9, CDKN2B, CDO1 and NANOG) was evaluated in 72 primary TGCT by quantitative methylation specific PCR...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881577/a-comprehensively-characterized-cell-line-panel-highly-representative-of-clinical-ovarian-high-grade-serous-carcinomas
#20
Kelsie L Thu, Mahboubeh Papari-Zareei, Victor Stastny, Kai Song, Michael Peyton, Victor D Martinez, Yu-An Zhang, Isabel B Castro, Marileila Varella-Garcia, Hanquan Liang, Chao Xing, Ralf Kittler, Sara Milchgrub, Diego H Castrillon, Heather L Davidson, C Patrick Reynolds, Wan L Lam, Jayanthi Lea, Adi F Gazdar
Recent literature suggests that most widely used ovarian cancer (OVCA) cell models do not recapitulate the molecular features of clinical tumors. To address this limitation, we generated 18 cell lines and 3 corresponding patient-derived xenografts predominantly from high-grade serous carcinoma (HGSOC) peritoneal effusions. Comprehensive genomic characterization and comparison of each model to its parental tumor demonstrated a high degree of molecular similarity. Our characterization included whole exome-sequencing and copy number profiling for cell lines, xenografts, and matched non-malignant tissues, and DNA methylation, gene expression, and spectral karyotyping for a subset of specimens...
August 1, 2017: Oncotarget
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