Figure 1: The cancer gene landscape of osteosarcoma.
The driver mutations of 112 osteosarcomas are shown in a. For each mutated cancer gene the percentage of 112 tumours with at least one driver mutation is shown, subdivided by mutation type. Blue: point mutation (substitutions; indels). Green: structural variant (amplification; homozygous deletion; disruptive breakpoint). (b) Driver events that were found in IGF1R signalling genes operative at the level of IGF1R. Blue square: amplification. Red circle: truncating mutation. An example of an amplicon is shown in c, found in case PD7193a. The x axis shows genomic position in mega bases and the y axis shows absolute copy number. Each dot in the plot represents the copy number of a particular genomic position. Lines and arcs: breakpoint with rearrangements coded by colour. Brown: tandem duplication; blue: deletion; green and turquoise: inversion; grey with arrowheads: interchromosomal rearrangement. (d) The key components of IGF signalling7,8,9. At the level of the cell membrane, IGF signalling is mediated by IGF1R. IGF2R is a nonsignalling receptor that acts as a negative regulator of IGF1R. A number of circulating binding proteins modulate the function of IGF1R signalling, including IGFBP5 that is thought to inhibit IGF1R. Note that both IGF1 and IGF2 have autocrine, paracrine as well as endocrine sources7,8,9.
