Date of Award

Spring 2004

Degree Type

Thesis - Restricted

Degree Name

Master of Science (MS)

Department

Mathematics

Abstract

A cDNA-microarray experiment was performed to study thyroid cancer metastasis. Follicular thyroid carcinoma cell lines from the primary (FTC-133) and lung metastasis (FTC-238) of the same patient were compared using a 19200 human cDNA micro array. Hybridizations were repeated with 3 separate cell passages, 3 repeats for each passage. Data were extracted and normalized for dye bias using commercial and house-developed software. Differential expression was determined by reference distribution method. Seven hundred seventy five genes and expressed sequence tags (ESTs) were identified as significantly over (393) /under (382) expressed (t test p < 0.05) with respect to metastatic vs. primary thyroid carcinoma. Using both software and manual expert annotation with a threshold of log2 ratio IEijl >2, 13119 over and 13/35 under expressed genes were associated with oncogenesis and/or metastatic processes. Six of the over expressed genes and four of the under expressed genes were further confirmed by realtime PCR. Western Blotting revealed protein over expression in 3 of3 genes tested. Several biological functional groups associated with the biological process (e.g. cell adhesion, cell migration, cell proliferation, apoptosis) of cancer metastasis were found to be affected. This study shows the feasibility of using high-throughput technologies for identifying genes and functional groups leading to metastatic follicular thyroid cancer. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.

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