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Molecular Portraits of Cancer

Molecular Portraits of Cancer. Microarrays and Cell Biology. Microarrays and Clustering. Microarrays provides a matrix of information correlated gene expression group GENES by similarity of expression pattern group CELLS by similarity of expression pattern

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Molecular Portraits of Cancer

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  1. Molecular Portraits of Cancer Microarrays and Cell Biology Karp/CELL & MOLECULAR BIOLOGY 3E

  2. Microarrays and Clustering • Microarrays • provides a matrix of information • correlated gene expression • group GENES by similarity of expression pattern • group CELLS by similarity of expression pattern • usually reorder rows and columns for presenting • Both genes, cells grouped by Cluster Analysis • Lots of different programs/methods for clustering Karp/CELL & MOLECULAR BIOLOGY 3E

  3. Microarrays and Clustering • Supervised clustering • Uses external information to guide clustering • Frequently used to “train” neural network algorithms • Sometimes “known” tumors used to “learn” pattern/portrait • Unsupervised clustering • Groups tumors based on similarity of gene expression • Usually some “vector analogy” applies • Both methods can be used to define and predict tumor types Karp/CELL & MOLECULAR BIOLOGY 3E

  4. Molecular Definition of Tumors • Tumors are individuals • Each tumor has its own unique gene expression pattern • Can be referred to as a “Molecular Portrait” • Even highly related tumors (same clone?) can show differences • sub-clonal diversity Karp/CELL & MOLECULAR BIOLOGY 3E

  5. Tumor Portraits • Arrays contain info about cell type of origin • Example: CNS tumors (Fig2) • Clear distinctions between CNS tumors • Medulogliomas likely derived from non-neural oligodendrocytes • Meduloblastomas (MD’s) from cerebellar granule cells • 50 gene set used to diagnose CNS tumor type • Improvement over predictions based on histology • PCA:“strongest” linear combination of genes Karp/CELL & MOLECULAR BIOLOGY 3E

  6. Full Gene Set Principle Components Analysis (3D) Best 50 Genes Karp/CELL & MOLECULAR BIOLOGY 3E

  7. Best 50 Genes Karp/CELL & MOLECULAR BIOLOGY 3E

  8. Tumor Portraits • Arrays contain info about developmental stage • Stage of development affects clinical behavior • DLBCL (diffuse, large B-cell lymphomas) • Germinal center B-cell-like (GCBL) • Activated B-cell-like (ABL) • Third type lacking pattern of other two • ALL subtypes found • Pro-T-cell • Early cortical thymocyte • Late cortical thymocyte Karp/CELL & MOLECULAR BIOLOGY 3E

  9. Tumor Portraits • Arrays contain info about prognosis • Meduloblastomas (MD’s) with or without metastasis • Metastasis was correlated with PDGF, ras, MAPK • Treatment can potentially be informed by primary tumor gene expression patterns • Predicting the future phenotype of the tumor Karp/CELL & MOLECULAR BIOLOGY 3E

  10. Tumor Portraits • Arrays reveal a common (cancer) imprint • Interferon gene set (3c) • Proliferation gene set (3g) • Basal epithelial gene set (3e) Karp/CELL & MOLECULAR BIOLOGY 3E

  11. Karp/CELL & MOLECULAR BIOLOGY 3E

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