Research Article

The Genomic Landscapes of Human Breast and Colorectal Cancers

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Science  16 Nov 2007:
Vol. 318, Issue 5853, pp. 1108-1113
DOI: 10.1126/science.1145720

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  1. Fig. 1.

    Clustering of somatic mutations in protein structures. Individual somatic mutations were mapped onto structural homology models on the basis of known crystal structure information. Homology models were built with MODPIPE (33) and graphics were created with UCSF Chimera software (34). Yellow spheres indicate mutated residues. (A) Two somatic mutations in the glycosylation enzyme GALNT5 occur in residues on different sides of the enzyme active site. Stick models indicate enzyme substrates. (B) Three somatic mutations in the transglutaminase TGM3 located at nearby surface regions of the protein (two mutations are present at the same residue on the right-hand side).

  2. Fig. 2.

    PI3K pathway mutations in breast and colorectal cancers. The identities and relationships of genes that function in PI3K signaling are indicated. Circled genes have somatic mutations in colorectal (red) and breast (blue) cancers. The number of tumors with somatic mutations in each mutated protein is indicated by the number adjacent to the circle. Asterisks indicate proteins with mutated isoforms that may play similar roles in the cell. These include insulin receptor substrates IRS2 and IRS4; phosphatidylinositol 3-kinase regulatory subunits PIK3R1, PIK3R4, and PIK3R5; and NF-κB regulators NFKB1, NFKBIA, and NFKBIE.

  3. Fig. 3.

    Cancer genome landscapes. Nonsilent somatic mutations are plotted in two-dimensional space representing chromosomal positions of RefSeq genes. The telomere of the short arm of chromosome 1 is represented in the rear left corner of the green plane and ascending chromosomal positions continue in the direction of the arrow. Chromosomal positions that follow the front edge of the plane are continued at the back edge of the plane of the adjacent row, and chromosomes are appended end to end. Peaks indicate the 60 highest-ranking CAN-genes for each tumor type, with peak heights reflecting CaMP scores (7). The dots represent genes that were somatically mutated in the individual colorectal (Mx38) (A) or breast tumor (B3C) (B) displayed. The dots corresponding to mutated genes that coincided with hills or mountains are black with white rims; the remaining dots are white with red rims. The mountain on the right of both landscapes represents TP53 (chromosome 17), and the other mountain shared by both breast and colorectal cancers is PIK3CA (upper left, chromosome 3).

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