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Malania M. Wilson

Bio: Malania M. Wilson is an academic researcher from Emory University. The author has contributed to research in topics: Survival analysis & Genotype. The author has an hindex of 6, co-authored 7 publications receiving 168 citations.

Papers
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Journal ArticleDOI
TL;DR: The protocol reported here is adapted from the Ambion RecoverAll Total Nucleic Acid Isolation Kit, but includes several modifications, and although the protocol focuses on DNA isolation, the RecoverAll Kit can also be utilized to recover RNA, including microRNA.
Abstract: Formalin-fixed, paraffin-embedded (FFPE) tissue is one of the most widely practiced methods for clinical sample preservation and archiving. It is estimated that, worldwide, over a billion tissue samples, most of them FFPE, are being stored in numerous hospitals, tissue banks, and research laboratories. These archived samples could potentially provide a wealth of information in retrospective molecular studies of diseased tissues. While standard for histopathology and microscopic investigation (e.g., hematoxylin and eosin [H&E] staining, immunohistochemistry [IHC], and tissue microarray [TMA]), FFPE samples pose a major challenge for molecular pathologists, because nucleic acids are heavily modified and trapped by extensive protein-nucleic acid and protein-protein cross linking. Historically, FFPE samples were not considered to be a viable source for molecular analyses. Recently, however, it has been discovered that with appropriate protease digestion, it is possible to release microgram amounts of DNA and RNA from FFPE samples. The purified nucleic acids, although highly fragmented, are suitable for a variety of downstream genomic and gene expression analyses, such as polymerase chain reaction (PCR), quantitative reverse transcription PCR (qRT-PCR), microarray, array comparative genomic hybridization (CGH), microRNA, and methylation profiling. Several commercial kits are currently available for FFPE extraction. The protocol reported here is adapted from the Ambion RecoverAll Total Nucleic Acid Isolation Kit, but includes several modifications. Although our protocol focuses on DNA isolation, the RecoverAll Kit can also be utilized to recover RNA, including microRNA.

40 citations

Journal ArticleDOI
TL;DR: N NAT2 status significantly modified the effects of alcohol and smoking on fecundability, emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health.

25 citations

Journal ArticleDOI
TL;DR: These preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies and show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting.
Abstract: The role of molecular methods in the diagnosis of head and neck cancer is rapidly evolving and holds great potential for improving outcomes for all patients who suffer from this diverse group of malignancies . However, there is considerable debate as to the best clinical approaches, particularly for Next Generation Sequencing (NGS). The choices of NGS methods such as whole exome, whole genome, whole transcriptomes (RNA-Seq) or multiple gene resequencing panels, each have strengths and weakness based on data quality, the size of the data, the turnaround time for data analysis, and clinical actionability. There have also been a variety of gene expression signatures established from microarray studies that correlate with relapse and response to treatment, but none of these methods have been implemented as standard of care for oropharyngeal squamous cell carcinoma (OPSCC). Because many genomic methodologies are still far from the capabilities of most clinical laboratories, we chose to explore the use of a combination of off the shelf targeted mutation analysis and gene expression analysis methods to complement standard anatomical pathology methods. Specifically, we have used the Ion Torrent AmpliSeq cancer panel in combination with the NanoString nCounter Human Cancer Reference Kit on 8 formalin-fixed paraffin embedded (FFPE) OPSCC tumor specimens, (4) HPV-positive and (4) HPV-negative. Differential expression analysis between HPV-positive and negative groups showed that expression of several genes was highly likely to correlate with HPV status. For example, WNT1, PDGFA and OGG1 were all over-expressed in the positive group. Our results show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting for clinical laboratories lacking the instrumentation or bioinformatics infrastructure to support comprehensive genomics workflows. To the best of our knowledge, these preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies. This reports serves as a proof of principle methodology in OPSCC.

23 citations

Journal ArticleDOI
TL;DR: The data suggest that genetic variability involving vascular resistance modifiers, such as endothelin-1, might play an important role, particularly in patients with hypoplastic left heart syndrome, which is a serious problem for single-ventricle patients.

17 citations


Cited by
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Journal ArticleDOI
TL;DR: A mechanism by which Fn can drive CRC is unveiled and FadA is identified as a potential diagnostic and therapeutic target for CRC.

1,481 citations

Journal ArticleDOI
TL;DR: A deeper understanding of disease will be realized that will allow its targeting with much greater therapeutic precision, and global sharing of more accurate genotypic and phenotypic data will accelerate the determination of causality for novel genes or variants.
Abstract: Precision medicine is a strategy for tailoring clinical decision making to the underlying genetic causes of disease. This Review describes how, despite the straightforward overall principles of precision medicine, adopting it responsibly into clinical practice will require many technical and conceptual hurdles to be overcome. Such challenges include optimized sequencing strategies, clinically focused bioinformatics pipelines and reliable metrics for the disease causality of genetic variants.

602 citations

Journal ArticleDOI
TL;DR: This review describes the recent technological developments in NGS applied to the field of oncology and a number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA- sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequenced to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy.
Abstract: Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.

332 citations

Journal Article
TL;DR: The results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms and suggest the development of targeted therapies for head and neck cancer may be hindered by complex mutational profiles.
Abstract: Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.

264 citations