Graduation Date

Summer 8-19-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Bhavana J. Dave

Abstract

Myelodysplastic syndromes (MDS) are acquired heterogeneous hematopoietic clonal disorders primarily seen in the adult and elderly populations that presents a variety of cellular morphologies in cell lineages, varying prognoses, and differences in overall survival (OS) between individual patients. The occurrence of MDS in the pediatric and young adult population, or those between the ages of 0 and 29, is slowly on the rise. Pediatric and elderly cases exhibit diverse cytogenetic findings with differences in OS. The characterization of the genetic landscape of pediatric MDS is limited and most studies detailing genetic changes have been conducted in adult MDS cases. In order to aid in therapeutic stratification for pediatric cases, the key genes involved in hematopoietic transformation must be deciphered. This study utilized comprehensive analysis including cytogenetic karyotyping, FISH, and high-resolution microarray techniques. With the use of multiple techniques, this study confirmed the rarity of MDS in the pediatric population, characterized the frequencies of hallmark cytogenetic abnormalities, and identified key aberrations observed at the genetic level. With the use of microarray, we were able to detect genomic aberrations in 33 genes including novel copy number changes in more than one case in the PRDM16, IRF4, MYH11, ALK, CDKN2B, PAX5, EXT2, and ERCC4 genes. The results from this study prove the importance of comprehensive testing utilizing a variety of techniques in distinguishing the most accurate genetic landscape of pediatric MDS. This information can be used to better equip the medical community in accurately diagnosing and providing prognostic implications for therapy and treatment.

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