William Lin

Date of Award

January 2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael Girardi

Subject Area(s)

Genetics

Abstract

Cutaneous T cell lymphoma (CTCL) is a heterogenous disease that can progress to leukemic involvement and is lethal in advanced stages. Toward a better understanding of the pathogenesis and identification of novel therapeutic targets in this malignancy of CD4+ T cells, we conducted an integrative high-resolution genomic analysis combining DNA and mRNA data, along with clinical information, from 24 CTCL patients with blood involvement. We further performed a consensus analysis, totaling 108 samples, that confirms and narrows key loci to produce one of the most comprehensive views of the CTCL genome to date. The most significant regions of alteration are amplifications on 8q and 17q and deletions on 17p and chromosome 10. We also discover specific focal amplifications containing KIT and EGFR, and adjacent to VEGFA, raising the possibility of targeted therapeutic interventions. Correlating with clinical phenotypes, we determine 17q25.1 amplification's association with resistance to skin disease improvement and nominate candidate targets in this locus. Finally, we identify a gene expression signature of immunosuppression among patients who developed infections and secondary malignancies. Overall, we determine patterns in the CTCL genome with implications for pathogenesis and immunosuppression that may focus future therapeutic developments and the genetic classification of CTCL.

Comments

This is an Open Access Thesis.

Download
Open Access

This Article is Open Access

Share

COinS