Tumor progression

1
Tumor progression
COLON CANCER - TUMOR PROGRESSION
2
Colon cancer - global view
First stage Total of 144 micro-dissected
samples Performed on Affymetrix GeneChip U133A
(22,283 probe-sets)
22 Normal colon 24 polyp 47 primary cancer 19
lung metastasis 16 liver metastasis 5 normal
lung 11 normal liver
3
Colon cancer PCA
First stage Total of 144 micro-dissected
samples Performed on Affymetrix GeneChip U133A
(22,283 probe-sets)
22 Normal colon 24 polyp 47 primary cancer 19
lung metastasis 16 liver metastasis 5 normal
lung 11 normal liver
1st PCA tissue 2nd PCA transformation 3rd
PCA muscle/connective contamination 2 of the
dominant signals are not relevant
4
SPIN MOTIVATION GLOBAL LAYOUT OF DATA IDENTIFY
RELEVANT SUBSETS OF GENES SHAPES OF DATA
CLOUDS DEMONSTRATE ON COLON CANCER DATA
5
4 points
Gene 2
Gene 1
6
project on y
7
project on x
8
PCA
Projection with Maximal Variance
9
Pitas.fig
10
PCA leukemia 1
Korsmeyer ALL,AML,MLL 8700 genes
Nature 2001
11
PCA Leukemia 2
Korsmeyer ALL,AML,MLL (In space of 500 most
separating genes)
12
Colon cancer PCA
First stage Total of 144 micro-dissected
samples Performed on Affymetrix GeneChip U133A
(22,283 probe-sets)
22 Normal colon 24 polyp 47 primary cancer 19
lung metastasis 16 liver metastasis 5 normal
lung 11 normal liver
1st PCA tissue 2nd PCA transformation 3rd
PCA muscle/connective contamination 2 of the
dominant signals are not relevant
13
Colon - 1,000 highest variance genes
14
Cervical Cancer - Gene Expression Matrix
5 Normal cervical tissues 35 Tumors (5
repeats) 5 Cancer cell lines
15
Focus on relevant samples
Removed the cell lines, the normals, the a6g
(29-3) that clustered with the normals kept 1 of
each repeat
16
4 points
17
toy distmat
(5) (19) (27) (37)
0.0 10.0 10.77 2.82 10.0
0.0 2.82 7.21 10.77
2.82 0.0 8.24 2.82 7.21
8.24 0.0
0.0 2.82 10.0 10.77
10.0 7.21 0.0 2.82
10.77 8.24 2.82 0.0
2.82 0.0 7.21 8.24


18
toy distmat ordered
(5) (19) (27) (37)
(5) (37) (19) (27)
0.0 10.0 10.77 2.82 10.0
0.0 2.82 7.21 10.77
2.82 0.0 8.24 2.82 7.21
8.24 0.0
0.0 2.82 10.0 10.77 2.82
0.0 7.21 8.24 10.0
7.21 0.0 2.82 10.77
8.24 2.82 0.0


19
Bittner Yakhini MDS
Aug 2000
20
glioblastoma
S Godard, G Getz, H Kobayashi, P Farmer, M
Delorenzi, M Nozaki, A-C Diserens, M-F Hamou,
P-Y Dietrich, J-G Villemure, R C. Janzer, P
Bucher, R Stupp, N de Tribolet, E Domany, M E.
Hegi
GLIOBLASTOMA
CLONTECH ARRAYS
1185 Genes, 36 Samples
12 Astrocytoma(II) 4 secondary GBM
17 Primary GlioBlastoMa 3 Cell Lines