Translational discoveries in multiple myeloma

CREATED: 200801220205 Speaker: A/P Chng Wee Joo, Dept of Medicine

** Background

• Hallmarks of cancers
• Complex molecular circuitry of a cancer cell, redundancies and crosstalk
• Linear studies of single pathway/single gene do not show the whole picture
• Make use of global studies using microarray
• Applications: class discovery, response prediction, marker identification
• Multiple myeloma, malignancy of B-cells -> abnormal copy number, translocation ** Identification of hyper diploid myeloma
• three colors per slide, can identify 3 chromosomes
• use chromosome 9, 11, 15 to identify H-MM
• easier to target cancer cells which are multiplying vs those which are dormant
• heterogeneity in H-MM patients based on clustering of expression profile
• Array-CGH to look for genetic basis of clusters ** Centrosome amplification in MM
• centrosomes involved in dividing the chromosomes in cell division
• prognostic factor which predicts survival rates independent of treatment
• analysis of four genes associated with centrosomes produces an index which can be used clinically ** Integrated Pan-omics Analysis
• input: DNA, RNA, proteins, TMA cytospin
• technology ** aCGH -> genomic gain/loss ** GEP -> transcriptional signature ** proteonomic (MS, Ab Array) -> protein signature
• analysis: pathway, GO, GSEA
• output ** Etiology (genetic basis of molecular phenotype) ** diagnosis and prognosis (clinically relevant subtypes and their molecular markers) ** therapy (deregulated pathways)
• validation