DOCSLIB.ORG

Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes Evidence Report/Technology Assessment Number 160 Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-02-0018 Prepared by: The Johns Hopkins University Evidence-based Practice Center, Baltimore, MD Investigators Luigi Marchionni, M.D., Ph.D. Renee F. Wilson, M.Sc. Spyridon S. Marinopoulos, M.D., M.B.A. Antonio C. Wolff, M.D. Giovanni Parmigiani, M.D. Eric B. Bass, M.D., M.P.H. Steven N. Goodman, M.D., M.H.S., Ph.D. AHRQ Publication No. 08-E002 January 2008 This report is based on research conducted by the Johns Hopkins University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0018). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment. This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders. Suggested Citation: Marchionni L, Wilson RF, Marinopoulos SS, Wolff AC, Parmigiani G, Bass EB, Goodman SN. Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes. Evidence Report/Technology Assessment No. 160. (Prepared by The Johns Hopkins University Evidence- based Practice Center under contract No. 290-02-0018). AHRQ Publication No. 08-E002. Rockville, MD: Agency for Healthcare Research and Quality. January 2008. The investigators have no relevant financial interests in the report. The investigators have no employment, consultancies, honoraria, or stock ownership or options, or royalties from any organization or entity with a financial interest or financial conflict with the subject matter discussed in the report. ii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. The Centers for Disease Control and Prevention (CDC) requested and provided funding for this report. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release. AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. We welcome comments on this evidence report. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by e-mail to [email protected]. Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director Director, Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Julie Louise Gerberding, M.D., M.P.H. Gurvaneet Randhawa, M.D., M.P.H. Director EPC Program Task Order Officer Centers for Disease Control and Prevention Agency for Healthcare Research and Quality Beth Collins Sharp, Ph.D., R.N. Director, EPC Program Agency for Healthcare Research and Quality iii Acknowledgments The Evidence-based Practice Center thanks Michael Oladubu, D.D.S. and Allison Jonas, for their assistance with literature searching and database management, and project organization; Aly Shogan for her assistance in completing the sections on economics; Brenda Zacharko for her assistance with budget matters, and for her assistance with final preparations of the report. The Center also wishes to thank Gurvaneet Randhawa, M.D., M.P.H., AHRQ Task Order Officer, for his efforts in guiding this project and coordination with the CDC EGAPP group. iv Structured Abstract Objective: To assess the evidence that three marketed gene expression-based assays improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early stage breast cancer. Data Sources: MEDLINE®, EMBASE, the Cochrane databases, test manufacturer Web sites, and information provided by manufacturers. Review Methods: We evaluated the evidence for three gene expression assays on the market; Oncotype DX™, MammaPrint® and the Breast Cancer Profiling (BCP or H/I ratio) test, and for gene expression signatures underlying the assays. We sought evidence on: (a) analytic performance of tests; (b) clinical validity (i.e., prognostic accuracy and discrimination); (c) clinical utility (i.e., prediction of treatment benefit); (d) harms; and (e) impact on clinical decision making and health care costs. Results: Few papers were found on the analytic validity of the Oncotype DX and MammaPrint tests, but these showed reasonable within-laboratory replicability. Pre-analytic issues related to sample storage and preparation may play a larger role than within-laboratory variation. For clinical validity, studies differed according to whether they examined the actual test that is currently being offered to patients or the underlying gene signature. Almost all of the Oncotype DX evidence was for the marketed test, the strongest validation study being from one arm of a randomized controlled trial (NSABP-14) with a clinically homogeneous population. This study showed that the test, added in a clinically meaningful manner to standard prognostic indices. The MammaPrint signature and test itself was examined in studies with clinically heterogeneous populations (e.g., mix of ER positivity and tamoxifen treatment) and showed a clinically relevant separation of patients into risk categories, but it was not clear exactly how many predictions would be shifted across decision thresholds if this were used in combination with traditional indices. The BCP test itself was examined in one study, and the signature was tested in a variety of formulations in several studies. One randomized controlled trial provided high quality retrospective evidence of the clinical utility of Oncotype DX to predict chemotherapy treatment benefit, but evidence for clinical utility was not found for MammaPrint or the H/I ratio. Three decision analyses examined the cost-effectiveness of breast cancer gene expression assays, and overall were inconclusive. Conclusions: Oncotype DX is furthest along the validation pathway, with strong retrospective evidence that it predicts distant spread and chemotherapy benefit to a clinically relevant extent over standard predictors, in a well-defined clinical subgroup with clear treatment implications. The evidence for clinical implications of using MammaPrint was not as clear as with Oncotype DX, and the ability to predict chemotherapy benefit does not yet exist. The H/I ratio test requires further validation. For all tests, the relationship of predicted to observed risk in different populations still needs further study, as does their incremental contribution, optimal implementation, and relevance to patients on current therapies. v Contents Executive Summary.........................................................................................................................1 Evidence Report………………………………………………………………………………….9 Chapter 1. Introduction ................................................................................................................11 Breast Cancer...........................................................................................................................11 Gene expression profiling..................................................................................................12 Breast Cancer Assays on the Market .......................................................................................13 RT-PCR..............................................................................................................................14
Load more

Recommended publications
  • Whole Genome Sequencing and Comparative Genomic Analysis Of
    Li et al. BMC Genomics (2020) 21:181 https://doi.org/10.1186/s12864-020-6593-1 RESEARCH ARTICLE Open Access Whole genome sequencing and comparative genomic analysis of oleaginous red yeast Sporobolomyces pararoseus NGR identifies candidate genes for biotechnological potential and ballistospores-shooting Chun-Ji Li1,2, Die Zhao3, Bing-Xue Li1* , Ning Zhang4, Jian-Yu Yan1 and Hong-Tao Zou1 Abstract Background: Sporobolomyces pararoseus is regarded as an oleaginous red yeast, which synthesizes numerous valuable compounds with wide industrial usages. This species hold biotechnological interests in biodiesel, food and cosmetics industries. Moreover, the ballistospores-shooting promotes the colonizing of S. pararoseus in most terrestrial and marine ecosystems. However, very little is known about the basic genomic features of S. pararoseus. To assess the biotechnological potential and ballistospores-shooting mechanism of S. pararoseus on genome-scale, the whole genome sequencing was performed by next-generation sequencing technology. Results: Here, we used Illumina Hiseq platform to firstly assemble S. pararoseus genome into 20.9 Mb containing 54 scaffolds and 5963 predicted genes with a N50 length of 2,038,020 bp and GC content of 47.59%. Genome completeness (BUSCO alignment: 95.4%) and RNA-seq analysis (expressed genes: 98.68%) indicated the high-quality features of the current genome. Through the annotation information of the genome, we screened many key genes involved in carotenoids, lipids, carbohydrate metabolism and signal transduction pathways. A phylogenetic assessment suggested that the evolutionary trajectory of the order Sporidiobolales species was evolved from genus Sporobolomyces to Rhodotorula through the mediator Rhodosporidiobolus. Compared to the lacking ballistospores Rhodotorula toruloides and Saccharomyces cerevisiae, we found genes enriched for spore germination and sugar metabolism.
    [Show full text]
  • ESM1 As a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma
    Author Manuscript Published OnlineFirst on July 29, 2019; DOI: 10.1158/1078-0432.CCR-19-0859 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ESM1 as a marker of macrotrabecular-massive hepatocellular carcinoma. Julien Calderaro1,2,3, Léa Meunier4, Cong Trung Nguyen2,3, Marouane Boubaya5, Stefano Caruso4, Alain Luciani2,3,6, Giuliana Amaddeo2,3,7, Hélène Regnault7, Jean-Charles Nault4,8,9 , Justine Cohen1,2,Frédéric Oberti10, Sophie Michalak11, Mohamed Bouattour12, Valérie Vilgrain18, Georges Philippe Pageaux14, Jeanne Ramos15, Nathalie Barget16, Boris Guiu17, Valérie Paradis13, Christophe Aubé19, Alexis Laurent20, Jean-Michel Pawlotsky2,3,22, Nathalie Ganne-Carrié4,8,9, Jessica Zucman-Rossi4,22,23, Olivier Seror24, Marianne Ziol4,9,25. 1. Assistance Publique-Hôpitaux de Paris, Département Pathologie, CHU Henri Mondor, F-94000 Créteil, France. 2. Université Paris-Est Créteil, Faculté de Médecine, Créteil, France. 3. Inserm, U955, Team 18, Créteil, France. 4. INSERM UMR-1162, génomique fonctionnelle des tumeurs solides, 75010, Paris, France 5. Unité de Recherche Clinique, AP-HP, Hôpital Universitaire Avicenne, Bobigny, France. 6. Assistance Publique-Hôpitaux de Paris, Service de Radiologie, CHU Henri Mondor, F-94000 Créteil, France 7. Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, CHU Henri Mondor, F-94000 Créteil, France. 8. Service d’Hépatologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-HP, 93143 Bondy, France, 9. Université Paris 13, Sorbonne Paris-Cité, Bobigny, France 10. Hépato-gastroentérologie et oncologie digestive, Centre Hospitalier Universitaire d'Angers, France. 11. Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Universitaire d'Angers, France. 12. Assistance Publique-Hôpitaux de Paris, Service d’Oncologie Digestive, Hôpital Universitaire Beaujon, France.
    [Show full text]
  • Genetic Testing for Breast Cancer Recurrence and Predictive, MPM 33.0
    Medical Policy Subject: Genetic Testing for Breast Cancer Recurrence and Predictive Medical Policy #: 33.0 Original Effective Date: 07/31/2019 Status: Reviewed Last Review Date: 11/18/2020 Disclaimer Refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage. This may not be a benefit on all plans or the plan may have broader or more limited benefits than those listed in this Medical Policy. PHS follows CMS LCDs, and other Medicare manuals to provide support for determining coverage. The providers are expected to provide appropriate documentation when requested to support coverage. This policy is not a replacement for the Medicare source materials that outline Medicare coverage requirements. Where there is a conflict between this policy and Medicare source materials, the Medicare source materials will apply. Coverage Determination Prior Authorization is required. Logon to Pres Online to submit a request: https://ds.phs.org/preslogin/index.jsp Content in this policy: 1. Oncotype-DX: 2. Oncotype DX® for Ductal Carcinoma in Situ (DCIS): 3. ENDOPredict®: 4. MammaPrint®: 5. Prosigna: 6. Breast Cancer Index (BCI): 1. Oncotype-DX: PHP is using LCA (A55230), MolDX: Oncotype DX® Breast Cancer Assay (A55230): Test coverage for patients with the following findings For Medicare, Medicaid and Commercial: • estrogen-receptor positive, node-negative carcinoma of the breast • estrogen-receptor positive micrometastases of carcinoma of the breast, and • estrogen-receptor positive breast carcinoma with 1-3 positive nodes
    [Show full text]
  • ONCOPANEL (Popv3)
    ONCOPANEL (POPv3) TEST INFORMATION BACKGROUND: Somatic genetic alterations in oncogenes and tumor-suppressor genes contribute to the pathogenesis and evolution of human cancers. These alterations can provide prognostic and predictive information and stratify cancers for targeted therapeutic information. We classify these alterations into five tiers using the following guidelines: Tier 1: The alteration has well-established published evidence confirming clinical utility in this tumor type, in at least one of the following contexts: predicting response to treatment with an FDA-approved therapy; assessing prognosis; establishing a definitive diagnosis; or conferring an inherited increased risk of cancer to this patient and family. Tier 2: The alteration may have clinical utility in at least one of the following contexts: selection of an investigational therapy in clinical trials for this cancer type; limited evidence of prognostic association; supportive of a specific diagnosis; proven association of response to treatment with an FDA-approved therapy in a different type of cancer; or similar to a different mutation with a proven association with response to treatment with an FDA-approved therapyin this type of cancer. Tier 3: The alteration is of uncertain clinical utility, but may have a role as suggested by at least one of the following: demonstration of association with response to treatment in this cancer type in preclinical studies (e.g., in vitro studies or animal models); alteration in a biochemical pathway that has other known, therapeutically-targetable alterations; alteration in a highly conserved region of the protein predicted, in silico, to alter protein function; or selection of an investigational therapy for a different cancer type.
    [Show full text]
  • Environmental Influences on Endothelial Gene Expression
    ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community.
    [Show full text]
  • Dietary Chemoprevention Studies in Preclinical Models of Prostate Cancer: Bioactive Lipids and Vitamin D
    Dietary Chemoprevention Studies in Preclinical Models of Prostate Cancer: Bioactive Lipids and Vitamin D. Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Justin Bruce Smolinski, B.S. Ohio State University Nutrition (OSUN) Graduate Program The Ohio State University 2010 Dissertation Committee: Professor Steven K. Clinton, Advisor Professor Charles L. Brooks Professor Kichoon Lee Professor Mark L. Failla i Copyright by Justin Bruce Smolinski 2010 ii ABSTRACT Epidemiological evidence suggests that prostate cancer can be modulated by diet. Data exists that implicate both bioactive lipids and the vitamin D/ calcium axis in prostate cancer pathogenesis. These data suggest that bioactive lipids such as omega-3 fatty acids protect against prostate cancer, whereas omega-6 fatty acids promote prostate cancer. Population studies also indicate that a diet high in vitamin D decreases prostate cancer risk while calcium increases risk for prostate cancer, possibly by lowering circulating levels of protective vitamin D. In contrast, recent epidemiological studies indicate that vitamin D does not protect against prostate cancer, indicating that the role of vitamin D and calcium in this disease process is far from established. Importantly, crucial animal experiments are lacking that may serve to provide mechanistic data for the roles of these nutrients. The objective of the first study conducted in this dissertation was to evaluate and compare prostate carcinogenesis in murine models that utilize the SV40 Tag transformation system- TRAMP and Apt121/Rbf. These are commonly used models in prostate cancer chemoprevention studies. We characterized these models with respect to time to tumor development, tumor size and metastasis.
    [Show full text]
  • Pdf Sub-Classification of Patients with a Molecular Alteration Provides Better Response [57]
    Theranostics 2021, Vol. 11, Issue 12 5759 Ivyspring International Publisher Theranostics 2021; 11(12): 5759-5777. doi: 10.7150/thno.57659 Research Paper Homeobox B5 promotes metastasis and poor prognosis in Hepatocellular Carcinoma, via FGFR4 and CXCL1 upregulation Qin He1, Wenjie Huang2, Danfei Liu1, Tongyue Zhang1, Yijun Wang1, Xiaoyu Ji1, Meng Xie1, Mengyu Sun1, Dean Tian1, Mei Liu1, Limin Xia1 1. Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. 2. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei, 430030, China. Corresponding author: Dr. Limin Xia, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China; Phone: 86 27 6937 8507; Fax: 86 27 8366 2832; E-mail: [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2020.12.29; Accepted: 2021.03.17; Published: 2021.03.31 Abstract Background: Since metastasis remains the main reason for HCC-associated death, a better understanding of molecular mechanism underlying HCC metastasis is urgently needed.
    [Show full text]
  • GALA, a Database for Genomic Sequence Alignments and Annotations
    Resources GALA, a Database for Genomic Sequence Alignments and Annotations Belinda Giardine,1 Laura Elnitski,1,2 Cathy Riemer,1 Izabela Makalowska,4 Scott Schwartz,1 Webb Miller,1,3,4 and Ross C. Hardison2,4,5 Departments of 1Computer Science and Engineering, 2Biochemistry and Molecular Biology, 3Biology, and 4Huck Institute for Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA We have developed a relational database to contain whole genome sequence alignments between human and mouse with extensive annotations of the human sequence. Complex queries are supported on recorded features, both directlyand on proximityamong them. Searches can reveal a wide varietyof relationships, such as finding all genes expressed in a designated tissue that have a highlyconserved non coding sequence !Ј to the start site. Other examples are finding single nucleotide polymorphisms that occur in conserved noncoding regions upstream of genes and identifying CpG islands that overlap the !Ј ends of divergentlytranscribed genes. The database is available online at http://globin.cse.psu.edu/ and http://bio.cse.psu.edu/. The determination and annotation of complete genomic combined with sequence conservation can refine predictions DNA sequences provide the opportunity for unprecedented of functional sequences (Levy et al. 2001). One way to do this advances in our understanding of evolution, genetics, and is to record both extensive annotations and sequence align- physiology, but the amount and diversity of data pose daunt- ments in a database. ing challenges as well. Three excellent browsers provide access We have developed a database of genomic DNA se- to the sequence and annotations of the human genome, viz., quence alignments and annotations, called GALA, to search the human genome browser !"#$ at %&'& (Kent et al.
    [Show full text]
  • ANSWER KEY Sybsc. Life Sciences- SEM
    ANSWER KEY S.Y.B.Sc. Life Sciences- SEM III - Paper III Q.P.Code: 79543 Exam Date: 2nd November 2018 Marks : 100 Q. 1 Do as Directed: (20mks) .Q. 1. A) Define / Explain the following terms: (07) 1. TCP/IP- It is commonly known as TCP/IP because the foundational protocols in the suite are the Transmission Control Protocol (TCP) and the Internet Protocol (IP). It is a set of networking protocols that allows two or more computers to communicate. 2. WWW- The World Wide Web (WWW), also called the Web, is an information space where documents and other web resourcesare identified by Uniform Resource Locators (URLs), interlinked by hypertext links, and accessible via the Internet. Web pages are primarily text documents formatted and annotated with Hypertext Markup Language (HTML). In addition to formatted text, web pages may contain images, video, audio, and software components that are rendered in the user's web browser as coherent pages of multimedia content. 3. Proteomics- Proteomics is the large-scale study of proteomes. A proteome is a set of proteins produced in an organism, system, or biological context. 4. Human Genome Project-The Genome Project (HGP) was an international scientific research project with the goal of determining the sequence of nucleotide base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint. 5. Forward reading frame-An open reading frame starts with an atg (Met) in most species and ends with a stop codon (taa, tag or tga).
    [Show full text]
  • Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
    www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1.
    [Show full text]
  • Annotating a Non-Model Plant Genome – a Study on the Narrow-Leafed Lupin
    BioTechnologia vol. 93(3) C pp. 318-332 C 2012 Journal of Biotechnology, Computational Biology and Bionanotechnology RESEARCH PAPER Annotating a non-model plant genome – a study on the narrow-leafed lupin ANDRZEJ ZIELEZIŃSKI 1, PIOTR POTARZYCKI 1, MICHAŁ KSIĄŻKIEWICZ 2, WOJCIECH M. KARŁOWSKI 1* 1 Laboratory of Computational Genomics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland 2 Institute of Plant Genetics, Polish Academy of Sciences, Poznan, Poland * Corresponding author: [email protected] Abstract We present here a highly portable and easy-to-use gene annotation system CEL (Computational Environment for annotation of Legume genomes) that can be used to annotate any type of genomic sequence -- from BAC ends to complete chromosomes. CEL’s core engine is modular and hierarchically organized with an open-source struc- ture, permitting maximum customization -- users can assemble an individualized annotation pipeline by selecting computational components that best suit their annotation needs. The tool is designed to speed up genomic ana- lyses and features an algorithm that substitutes for a biologist’s expertise at various steps of gene structure pre- diction. This allows more complete automation of the labor-intensive and time-consuming annotation process. The system collects and prioritizes multiple sources of de novo gene predictions and gene expression evidence according to the confidence value of underlying supporting evidence, as a result producing high-quality gene- model sets. The data produced by CEL pipeline is suitable for direct visualization in any genome browser tool that supports GFF annotation format (e.g. Apollo, Artemis, Genome Browser etc.). This provides an easy means to view and edit individual contigs and BACs using just mouse’s clicks and drag-and-drop features.
    [Show full text]
  • Breast Cancer Recurrence Assay (Mammaprint®) Hs-197
    BREAST CANCER RECURRENCE ASSAY (MAMMAPRINT®) HS-197 Easy Choice Health Plan, Inc. Harmony Health Plan of Illinois, Inc. Missouri Care, Inc. ‘Ohana Health Plan, a plan offered by WellCare Health Insurance of Arizona, Inc. WellCare Health Insurance of Illinois, Inc. WellCare Health Plans of New Jersey, Inc. WellCare Health Insurance of Arizona, Inc. WellCare of Florida, Inc. WellCare of Connecticut, Inc. WellCare of Georgia, Inc. WellCare of Kentucky, Inc. Breast Cancer Recurrence WellCare of Louisiana, Inc. Assay (MammaPrint®) WellCare of New York, Inc. (Medicaid Only) WellCare of South Carolina, Inc. Policy Number: HS-197 WellCare of Texas, Inc. WellCare Prescription Insurance, Inc. Original Effective Date: 12/1/2011 Windsor Health Plan Revised Date(s): 8/2/2012; 10/4/2012; Windsor Rx Medicare Prescription Drug Plan 5/2/2013; 4/3/2014; 4/2/2015 APPLICATION STATEMENT The application of the Clinical Coverage Guideline is subject to the benefit determinations set forth by the Centers for Medicare and Medicaid Services (CMS) National and Local Coverage Determinations and state-specific Medicaid mandates, if any. BREAST CANCER RECURRENCE ASSAY (MAMMAPRINT®) HS-197 DISCLAIMER The Clinical Coverage Guideline is intended to supplement certain standard WellCare benefit plans. The terms of a member’s particular Benefit Plan, Evidence of Coverage, Certificate of Coverage, etc., may differ significantly from this Coverage Position. For example, a member’s benefit plan may contain specific exclusions related to the topic addressed in this Clinical Coverage Guideline. When a conflict exists between the two documents, the Member’s Benefit Plan always supersedes the information contained in the Clinical Coverage Guideline.
    [Show full text]