Gene expression analysis in DLBCL; Identification and characterization of novel proteins
Year: 2008
Type: dissertation
Abstract: Follicular lymphoma (FL) represents the most common low-grade Non-Hodgkin’s lymphoma. FLs are of B cell origin, generally incurable, and frequently transform to high-grade diffuse large B cell lymphoma (DLBCL). Transformation is generally correlated with poor prognosis and the molecular mechanisms involved are largely unknown. The present study aimed at the identification of novel genes that were differentially expressed in patient-matched biopsies of FL and DLBCL to increase the understanding of disease progression. \n \nApplication of the subtraction methodology cDNA Representational Difference Analysis (cDNA RDA) on lymphoma biopsies identified 92 differentially expressed genes. Of these, two novel genes were characterized: the Immunoglobulin-like domain containing receptor 1 gene (ILDR1) and the centrosome/spindle pole-associated protein 1 gene (CSPP1). ILDR1 encodes three isoforms and upon examination of a limited set of biopsies, one of the isoforms showed a lymphoma-associated expression. Over-expression of CSPP disturbs spindle assembly and impairs progression through the G1/S phase of the cell cycle. A correlation between CSPP1 mRNA over-expression and poor prognosis in a larger set of de novo DLBCLs in conjunction with the mitotic defects observed upon over-expression in vitro, suggests that CSPP is involved in cell-cycle control and cancer development/progression. A novel gene family, the family with sequence similarity 110 (FAM110), consisting of members A, B, and C were identified as potential interaction partners to CSPP. Also these proteins associate with centrosomes and spindle poles and arrest cells in the G1 phase upon over-expression, thereby indicating a role in cell-cycle control. Furthermore, FAM110C localizes to the microtubule cytoskeleton, and depletion of this protein impairs cell spreading and migration of epithelial cells.
Author: Helena Hauge
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2400506162