Parental DHFR* integration sites and copy number aberrations in methotrexate resistant colonies. (a) Copy number profile of cell line HCT116+chr3 and positions of 13 DHFR* integrations. This near-diploid cell line is characterized by partial chromosomal gains on chromosomes 3, 8, 10, 12, 16, losses on chromosomes 4, 16 and 10 and homozygous deletion on chromosome 16. Shown are the log2 ratios on BAC clones ordered according to genome position (UCSC Genome Browser, May 2004 freeze). Arrows indicate the positions of integration of one copy of DHFR* as mapped by inverse PCR to the human genome sequence. (b) Heatmap representation of copy number changes detected by array CGH in 82 methotrexate resistant colonies from 12 different insertion sites. Each column represents one resistant colony. Resistant colonies from each DHFR* integration site were clustered according to their copy number changes. Positions of the insertion sites are indicated by the arrowheads. Individual BAC clones are shown as rows and ordered according to their genome position (UCSC Genome Browser, May 2004 freeze). Copy number losses are indicated in red, gains in green and amplifications as yellow dots.