Biomedical subjects

Mary E Edgerton

Publications and source records attributed to Mary E Edgerton.

5 recordsLinked to original sources

PubMed2005

Using prior knowledge and rule induction methods to discover molecular markers of prognosis in lung cancer.

An iterative computational scientific discovery approach is proposed and applied to gene expression data for resectable lung adenocarcinoma patients. We use genes learned from the C5.0 rule induction algorithm, clinical features and prior knowledge derived from a network of interacting genes as represented in a database obtained with PathwayAssist to discover markers for prognosis in the gene expression data. This is done in an iterative fashion with machine learning techniques seeding the prior knowledge. This research illustrates the utility of combining signaling networks and machine learning techniques to produce simple prognostic classifiers.

Adenocarcinoma↗

PubMed2004

Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression.

Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit alpha (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We sought to determine at what stage of tumor development gene copy number increase or phosphorylated Akt overexpression might affect tumor development. We assessed PIK3CA gene copy number by fluorescence in situ hybridization and expression of phosphorylated Akt by immunohistochemistry in 242 invasive and 43 preinvasive lung cancers and correlated our findings with clinical outcome. The PIK3CA was amplified in 70% of squamous carcinomas, 38% of large cell carcinomas, 19% of adenocarcinomas, and 67% of small cell lung cancers. Phosphorylated Akt overexpression was frequently observed, and strongly so in 12 to 17% of lung cancers depending on nuclear or cytoplasmic localization. Neither PIK3CA gene copy number nor phosphorylated Akt protein expression had prognostic significance. In preinvasive lesions, amplification of the PIK3CA and overexpression of phosphorylated Akt were associated with severe dysplasia and each other. These observations suggest frequent and early involvement of the PI3-kinase pathway in lung cancer.

Aged↗

PubMed2003

Significance of p63 amplification and overexpression in lung cancer development and prognosis.

The fight against lung cancer is greatly compromised by the lack of effective early detection strategies. Genomic abnormalities and specifically the amplification of chromosomal region 3q26-3qter in lung cancer represent a major signature of neoplastic transformation. Here, we address the significance of p53 homologue p63 mapping to 3q27 in lung tumorigenesis. We analyzed p63 gene copy number (CN) by fluorescence in situ hybridization and expression by immunohistochemistry in tissue microarrays of 217 non-small cell lung cancers (NSCLCs) and correlated them with survival. We additionally characterized our findings in a subset of 24 NSCLCs by reverse transcription-PCR and Western blotting. We analyzed p63 CN and protein expression in 41 preinvasive squamous lesions. The p63 genomic sequence was amplified in 88% of squamous carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was DeltaNp63alpha. Western analyses revealed DeltaNp63alpha expression in normal bronchus and squamous carcinomas but not in normal lung or in adenocarcinomas. Furthermore, p63genomic amplification and protein staining intensity associated with better survival. We found a significant increase in CN in preinvasive lesions graded severe dysplasia or higher. Our data demonstrate that there is early and frequent genomic amplification of p63 in the development of squamous carcinoma of the lung and that patients with NSCLC showing amplification and overexpression of p63 have prolonged survival. These observations suggest that p63 genomic amplification has an early role in lung tumorigenesis and deserves additional evaluation as a biomarker for lung cancer progression.

Alternative Splicing↗

PubMed2003

The tissue microarray data exchange specification: a community-based, open source tool for sharing tissue microarray data.

BACKGROUND: Tissue Microarrays (TMAs) allow researchers to examine hundreds of small tissue samples on a single glass slide. The information held in a single TMA slide may easily involve Gigabytes of data. To benefit from TMA technology, the scientific community needs an open source TMA data exchange specification that will convey all of the data in a TMA experiment in a format that is understandable to both humans and computers. A data exchange specification for TMAs allows researchers to submit their data to journals and to public data repositories and to share or merge data from different laboratories. In May 2001, the Association of Pathology Informatics (API) hosted the first in a series of four workshops, co-sponsored by the National Cancer Institute, to develop an open, community-supported TMA data exchange specification. METHODS: A draft tissue microarray data exchange specification was developed through workshop meetings. The first workshop confirmed community support for the effort and urged the creation of an open XML-based specification. This was to evolve in steps with approval for each step coming from the stakeholders in the user community during open workshops. By the fourth workshop, held October, 2002, a set of Common Data Elements (CDEs) was established as well as a basic strategy for organizing TMA data in self-describing XML documents. RESULTS: The TMA data exchange specification is a well-formed XML document with four required sections: 1) Header, containing the specification Dublin Core identifiers, 2) Block, describing the paraffin-embedded array of tissues, 3)Slide, describing the glass slides produced from the Block, and 4) Core, containing all data related to the individual tissue samples contained in the array. Eighty CDEs, conforming to the ISO-11179 specification for data elements constitute XML tags used in the TMA data exchange specification. A set of six simple semantic rules describe the complete data exchange specification. Anyone using the data exchange specification can validate their TMA files using a software implementation written in Perl and distributed as a supplemental file with this publication. CONCLUSION: The TMA data exchange specification is now available in a draft form with community-approved Common Data Elements and a community-approved general file format and data structure. The specification can be freely used by the scientific community. Efforts sponsored by the Association for Pathology Informatics to refine the draft TMA data exchange specification are expected to continue for at least two more years. The interested public is invited to participate in these open efforts. Information on future workshops will be posted at http://www.pathologyinformatics.org (API we site).

Community Health Services↗

PubMed2002

A bioinformatics tool to select sequences for microarray studies of mouse models of oncogenesis.

UNLABELLED: One of the challenges to the effective utilization of cDNA microarray analysis in mouse models of oncogenesis is the choice of a critical set of probes that are informative for human disease. Given the thousands of genes with a potential role in human oncogenesis and the hundreds of thousands of mouse sequences available for use as probes, selection of an informative set of mouse probes can be an overwhelming task. We have developed a web based sequence mining tool using DataBase Independent (DBI) Perl to annotate publicly available sequences. The Mouse Oncochip Design Tool uses the Mouse Genome Database (MGD) developed and maintained by the Jackson Laboratories for mouse DNA sequences. There are over 380 000 sequences in their database. The output list has been ordered to present the genes more likely to be informative in a mouse model of human cancer using a candidate set of oncogenes to order the list. Mouse sequences that represent genes that are homologous with a member of a human oncogene set are listed first. In addition it provides a set of links for information on clone source gene function. CONTACT: http://nciarray.nci.nih.gov/cgi-bin/me/mouse_design.cgi

Animals↗