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https://www.readbyqxmd.com/read/29774112/rare-genetic-heterogeneity-within-single-tumor-discovered-for-the-first-time-in-colorectal-liver-metastases-after-liver-resection
#1
Mylène Sebagh, Nelly Bosselut, Alexandre Dos Santos, Marc-Antoine Allard, Aldrick Ruiz, Raphaël Saffroy, Daniel Cherqui, Eric Vibert, Denis Castaing, René Adam, Antonio Sa Cunha, Antoinette Lemoine
Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771009/primary-tumor-sidedness-is-an-independent-prognostic-marker-for-survival-in-metastatic-colorectal-cancer-results-from-a-large-retrospective-cohort-with-mutational-analysis
#2
Sophia C Kamran, Jeffrey W Clark, Hui Zheng, Darrell R Borger, Lawrence S Blaszkowsky, Jill N Allen, Eunice L Kwak, Jennifer Y Wo, Aparna R Parikh, Ryan D Nipp, Janet E Murphy, Lipika Goyal, Andrew X Zhu, A John Iafrate, Ryan B Corcoran, David P Ryan, Theodore S Hong
Recent reports demonstrate inferior outcomes associated with primary right-sided vs left-sided colorectal tumors in patients with metastatic colorectal cancer (mCRC). We sought to describe our experience with mCRC patients on whom we have molecular data to determine whether primary tumor sidedness was an independent prognostic marker for overall survival (OS). mCRC patients with documented primary tumor sidedness who received mutational profiling between 2009 and 2014 were identified (n = 367, median follow-up 30...
May 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29766551/lower-lip-capillary-malformation-associated-with-lymphatic-malformation-without-overgrowth-part-of-the-spectrum-of-clapo-syndrome
#3
Camila Downey, Juan Carlos López-Gutiérrez, Esther Roé-Crespo, Luis Puig, Eulalia Baselga
Characteristic lower lip capillary malformation of CLAPO syndrome (Capillary malformation of the lower lip, Lymphatic malformations of the face and neck, Asymmetry, and Partial or generalized Overgrowth) may also occur as an isolated lesion or with only minor anomalies, supporting the concept that there is a spectrum of abnormalities in CLAPO syndrome. Preliminary studies have demonstrated mosaic activating mutations in PIK3CA.
May 15, 2018: Pediatric Dermatology
https://www.readbyqxmd.com/read/29765551/functional-significance-of-co-occurring-mutations-in-pik3ca-and-map3k1-in-breast-cancer
#4
Alvaro Avivar-Valderas, Robert McEwen, Amir Taheri-Ghahfarokhi, Larissa S Carnevalli, Elizabeth L Hardaker, Marcello Maresca, Kevin Hudson, Elizabeth A Harrington, Francisco Cruzalegui
The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2 ), decreased function in tumor suppressors (e.g. PTEN ) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinases of the JNK apoptotic pathway in luminal A BrCa samples...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765547/signature-program-a-platform-of-basket-trials
#5
Eric D Slosberg, Barinder P Kang, Julio Peguero, Matthew Taylor, Todd M Bauer, Donald A Berry, Fadi Braiteh, Alexander Spira, Funda Meric-Bernstam, Steven Stein, Sarina A Piha-Paul, August Salvado
Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#6
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761914/molecular-features-in-young-vs-elderly-breast-cancer-patients-and-the-impacts-on-survival-disparities-by-age-at-diagnosis
#7
Mei-Xia Wang, Jun-Ting Ren, Lu-Ying Tang, Ze-Fang Ren
Young and elderly breast cancer patients are more likely to have a poorer outcome than middle-aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four-step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53, PIK3CA, MLL3, CDH1, GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29755687/clinical-application-of-targeted-next-generation-sequencing-for-colorectal-cancer-patients-a-multicentric-belgian-experience
#8
Nicky D'Haene, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon, Marie Le Mercier
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755676/genetic-heterogeneity-and-actionable-mutations-in-her2-positive-primary-breast-cancers-and-their-brain-metastases
#9
Leticia De Mattos-Arruda, Charlotte K Y Ng, Salvatore Piscuoglio, Maria Gonzalez-Cao, Raymond S Lim, Maria R De Filippo, Nicola Fusco, Anne M Schultheis, Carolina Ortiz, Santiago Viteri, Alexandra Arias, Gabriel S Macedo, Mafalda Oliveira, Patricia Gomez, Cristina Teixidó, Paolo Nuciforo, Vicente Peg, Cristina Saura, Santiago Ramon Y Cajal, Francesc Tresserra Casas, Britta Weigelt, Javier Cortes, Joan Seoane, Jorge S Reis-Filho
Brain metastases constitute a challenge in the management of patients with HER2-positive breast cancer treated with anti-HER2 systemic therapies. Here we sought to define the repertoire of mutations private to or enriched for in HER2-positive brain metastases. Massively parallel sequencing targeting all exons of 254 genes frequently mutated in breast cancers and/or related to DNA repair was used to characterize the spatial and temporal heterogeneity of HER2-positive breast cancers and their brain metastases in six patients...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755662/hotspot-kras-exon-2-mutations-in-cd166-positive-colorectal-cancer-and-colorectal-adenoma-cells
#10
Hung Lai Wong, Lawrence Po Wah Ng, Su Pin Koh, Lawrence Wing Chi Chan, Evelyn Yin Kwan Wong, Vivian Weiwen Xue, Hin Fung Andy Tsang, Amanda Kit Ching Chan, Ka Yue Chiu, Wah Cheuk, Sze Chuen Cesar Wong
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Recent studies have shown that cancer stem cells (CSCs) are an important cause of tumor recurrence and metastasis. We hypothesized that CSCs marker CD166-positive CRC and colorectal adenoma (CAD) cells consist of more hotspot mutations than CD166-negative CRC and colorectal adenoma cells. To verify this, formalin fixed paraffin embedded tissue specimens from 42 patients each with CRC and CAD were recruited and CD166 immunohistochemical (IHC) staining followed by macrodissection was performed...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752895/adaptation-of-an-amplicon-based-human-cancer-next-generation-sequencing-panel-assay-for-murine-tumors
#11
David R Meier, Kristopher A Lofgren, Grzegorz T Gurda, Paraic A Kenny
Unlike humans, inbred genetically engineered mice have minimal inter-individual variation and, consequently, offer substantially increased statistical power for robust definition of recurrent cooperating cancer mutations. While technically feasible, whole exome sequencing is expensive and extremely data-intensive. Somatic mutation analysis using panels of 25-75 genes now provides detailed insight into the biology of human tumors. Here we report an adaptation for mouse tumors of a human PCR amplicon-based panel (Ion Torrent Cancer Hotspot Panel v2) allowing analysis of 18 cancer genes, including Kras, Nras, Hras, Pten, Pik3ca and Smad4, and encompassing regions homologous to more than 2000 known human cancer mutations...
May 9, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29748010/canadian-cancer-trials-group-cctg-ind211-a-randomized-trial-of-pelareorep-reolysin-in-patients-with-previously-treated-advanced-or-metastatic-non-small-cell-lung-cancer-receiving-standard-salvage-therapy
#12
Penelope A Bradbury, Donald G Morris, Garth Nicholas, Dongsheng Tu, Moustapha Tehfe, John R Goffin, Frances A Shepherd, Richard W Gregg, Jeffrey Rothenstein, Christoper Lee, Sara Kuruvilla, Bruce D Keith, Vamsee Torri, Normand Blais, Desiree Hao, Grzegorz J Korpanty, Glenwood Goss, Barbara L Melosky, Mihaela Mates, Natasha Leighl, Jean-Pierre Ayoub, Joana Sederias, Harriet Feilotter, Lesley Seymour, Scott A Laurie
OBJECTIVES: Pelareorep (reolysin), a Dearing strain of reovirus serotype 3, has demonstrated oncolytic activity as single agent and synergy with chemotherapy. We evaluated pelareorep, combined with standard second-line chemotherapy in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This randomized phase II trial enrolled patients with advanced or metastatic NSCLC after first line chemotherapy. After a safety run-in, patients were randomized 1:1 to chemotherapy (pemetrexed [500 mg/m2, non-squamous], or docetaxel [75 mg/m2], day 1 every 21 days]) +/- pelareorep (4...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29747488/investigating-the-feasibility-of-targeted-next-generation-sequencing-to-guide-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#13
Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Purpose: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. Materials and Methods: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×...
May 9, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29739933/recurrent-hotspot-mutations-in-hras-q61-and-pi3k-akt-pathway-genes-as-drivers-of-breast-adenomyoepitheliomas
#14
Felipe C Geyer, Anqi Li, Anastasios D Papanastasiou, Alison Smith, Pier Selenica, Kathleen A Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M Schultheis, Luciano G Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R Lozada, Pedro Blecua, Simone Muenst, Achim A Jungbluth, Maria P Foschini, Hannah Y Wen, Edi Brogi, Juan Palazzo, Brian P Rubin, Charlotte K Y Ng, Larry Norton, Zsuzsanna Varga, Ian O Ellis, Emad A Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S Reis-Filho
Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRASQ61R in non-malignant ER-negative breast epithelial cells with or without a PIK3CAH1047R somatic knock-in results in transformation and the acquisition of the cardinal features of adenomyoepitheliomas, including the expression of myoepithelial markers, a reduction in E-cadherin expression, and an increase in AKT signaling...
May 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29739401/limited-utility-of-tissue-micro-arrays-in-detecting-intra-tumoral-heterogeneity-in-stem-cell-characteristics-and-tumor-progression-markers-in-breast-cancer
#15
Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga
BACKGROUND: Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29738578/cancer-driver-mutation-prediction-through-bayesian-integration-of-multi-omic-data
#16
Zixing Wang, Kwok-Shing Ng, Tenghui Chen, Tae-Beom Kim, Fang Wang, Kenna Shaw, Kenneth L Scott, Funda Meric-Bernstam, Gordon B Mills, Ken Chen
Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels...
2018: PloS One
https://www.readbyqxmd.com/read/29734916/carpal-tunnel-syndrome-in-aberrant-muscle-syndrome-a-case-report-and-review-of-the-literature
#17
Jessica Steele, Christopher Coombs
Aberrant Muscle Syndrome (AMS) is a rare congenital hand difference that is characterised by unilateral non-progressive muscular hyperplasia. The aetiology of aberrant muscle syndrome is not known, but a recently published case has shown a somatic PIK3CA activating mutation in a patient with AMS. Carpal tunnel syndrome (CTS) in children is rare. The most common causes are the mucopolysaccaridoses but space-occupying lesions have also been reported to cause CTS in children. We report the first case of CTS in a child with AMS successfully treated with open carpal tunnel release and excision of aberrant muscles...
June 2018: Journal of Hand Surgery Asian-Pacific Volume
https://www.readbyqxmd.com/read/29725898/rates-of-tp53-mutation-are-significantly-elevated-in-african-american-patients-with-gastric-cancer
#18
Elke J A H van Beek, Jonathan M Hernandez, Debra A Goldman, Jeremy L Davis, Kaitlin McLaughlin, R Taylor Ripley, Teresa S Kim, Laura H Tang, Jaclyn F Hechtman, Jian Zheng, Marinela Capanu, Nikolaus Schultz, David M Hyman, Marc Ladanyi, Michael F Berger, David B Solit, Yelena Y Janjigian, Vivian E Strong
BACKGROUND: Gastric adenocarcinoma is a heterogenous disease that results from complex interactions between environmental and genetic factors, which may contribute to the disparate outcomes observed between different patient populations. This study aimed to determine whether genomic differences exist in a diverse population of patients by evaluating tumor mutational profiles stratified by race. METHODS: All patients with gastric adenocarcinoma between 2012 and 2016 who underwent targeted next-generation sequencing of cancer genes by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform were identified...
May 3, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29720878/-egfr-kras-braf-pten-and-pik3ca-mutation-in-plasma-of-small-cell-lung-cancer-patients
#19
Hong-Yang Lu, Jing Qin, Na Han, Lei Lei, Fajun Xie, Chenghui Li
Background: Small cell lung cancer (SCLC) is an aggressive and deadly neuroendocrine tumor derived from bronchial epithelial cells. Although it results in a 95% mortality rate, the development of targeted therapies for SCLCs has lagged behind. The aim of this study is to better research mutation characteristics of SCLC and identify potential biomarkers for target therapy. Methods: We utilized high-resolution melting analysis to identify the mutations in epidermal growth factor receptor ( EGFR ), Kirsten rat sarcoma viral oncogene ( KRAS ), v-raf murine sarcoma viral oncogene homolog B1 ( BRAF ), phosphatase and tensin homolog ( PTEN ), and phosphatidylinositol-3-kinase catalytic ( PIK3CA ) from the blood...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29719410/oncogene-mutational-analysis-in-chinese-gastrointestinal-stromal-tumor-patients
#20
Qiong Chen, Rong Li, Zhi-Gao Zhang, Qiao-Ting Deng, Kun Li, Hao Wang, Xue-Xi Yang, Ying-Song Wu
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and exhibit a high frequency of oncogenic KIT or PDGFRA mutations. Tyrosine kinase inhibitors (TKIs) have been mainly used in the treatment of GISTs bearing KIT/PDGFRA mutations. However, other mutation profiles have been found to affect the sensitivity to and effectiveness of TKIs in the treatment of GISTs. Purpose: The aim of the present study was to describe the mutational status of multiple genes in GIST samples and to provide information for finding potential predictive markers of therapeutic targets in Chinese GIST patients...
2018: OncoTargets and Therapy
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