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Retrospective Transcriptional and Ge...

Di Cesare, Sebastian.

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Retrospective Transcriptional and Genomic Analysis of Formalin-Fixed Paraffin-Embedded Human Uveal Melanoma.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Retrospective Transcriptional and Genomic Analysis of Formalin-Fixed Paraffin-Embedded Human Uveal Melanoma./
作者:	Di Cesare, Sebastian.
面頁冊數:	152 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page: .
Contained By:	Dissertation Abstracts International72-09B.
標題:	Health Sciences, Pathology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR74419
ISBN:	9780494744192

Retrospective Transcriptional and Genomic Analysis of Formalin-Fixed Paraffin-Embedded Human Uveal Melanoma.
Di Cesare, Sebastian.

Retrospective Transcriptional and Genomic Analysis of Formalin-Fixed Paraffin-Embedded Human Uveal Melanoma. - 152 p.

Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page: .

Thesis (Ph.D.)--McGill University (Canada), 2011.

Many of the underlying genetic causes of Uveal Melanoma (UM) metastatic disease still remain to be elucidated. This particular cancer is the most common primary malignant intraocular tumor in adults, comprising approximately 5% of all diagnosed melanoma cases. Despite its rarity, approximately 50% of patients diagnosed with UM will develop metastatic disease. Due to the poor understanding of the genetic mechanisms that cause UM metastatic disease, further investigations into elucidating these mechanisms are necessary.

ISBN: 9780494744192Subjects--Topical Terms:

1017854
Health Sciences, Pathology.

Retrospective Transcriptional and Genomic Analysis of Formalin-Fixed Paraffin-Embedded Human Uveal Melanoma.
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502 $a Thesis (Ph.D.)--McGill University (Canada), 2011.
520 $a Many of the underlying genetic causes of Uveal Melanoma (UM) metastatic disease still remain to be elucidated. This particular cancer is the most common primary malignant intraocular tumor in adults, comprising approximately 5% of all diagnosed melanoma cases. Despite its rarity, approximately 50% of patients diagnosed with UM will develop metastatic disease. Due to the poor understanding of the genetic mechanisms that cause UM metastatic disease, further investigations into elucidating these mechanisms are necessary.
520 $a Fresh biopsied ocular tumor tissues are difficult to obtain for the purpose of performing microarray experiments on extracted nucleic acids. Present technology now allows for extraction of total RNA from formalin-fixed paraffin embedded (FFPE) tissue to run genomic cancer arrays by the cDNA mediated Annealing Sectioning and Ligation (DASL) method. We aimed to correlate gene transcript differences between two UM clinical-histopathological parameters (Metastasis, Cell Type). ANOVA testing identified 106 genes with a significant change in transcript abundance (p < 0.05, Welch T-test) between tumors from patients that died of metastasis to those that did not. Similarly, 64 genes significantly differed in transcript abundance when the spindle and epithelioid cell type parameters were compared. As a predictor of metastasis-dependant death, 12 genes were shown to correctly predict this parameter in 27/37 tumors (73%). As a predictor of UM cell type we successfully predicted the classification of 27/31 (87.1%) non-mixed tumors with a significant difference in transcript abundance between 10 genes.
520 $a We sought to validate these transcriptional findings at the DNA and protein level using comparative genomic hybridization arrays (aCGH) and immunohistochemistry. LIG4 (predictor of metastasis) and ErbB3 (predictor of UM cell type) correlated well at both levels in independent patient sample populations.
520 $a In addition, DASL analysis revealed an up-regulation of PAI-1 serum bio-marker expression in patients that developed metastatic disease. ELISA analysis of UM patient plasma revealed a positive correlation of increased PAI-1 plasma protein expression with increasing tumor height (n = 11, r = 0.6525, p = 0.0295).
520 $a To the best of our knowledge, this is the first study to have performed and validated a retrospective transcriptional analysis using RNA extracted from FFPE primary UM.
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